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Mitochondria importance articles
Abstract-level scientific briefs on mitochondria preprints—structured for researchers and agents. Free in the browser. Machine JSON remains available via x402 for bots.
176 articles · updated 2026-09-18T14:04Z
- biorxiv2026-09-08score 94mtDNAtherapeuticsmetabolism
A TYMP mRNA-lipid nanoparticle resets blood nucleosides in a mitochondrial DNA depletion syndrome within hours
Mitochondrial neurogastrointestinal encephalomyopathy is a thymidine-phosphorylase failure that poisons mitochondrial nucleotide pools systemically. Intravenous human TYMP mRNA in lipid nanoparticles puts the enzyme in mouse liver, is tolerated, and returns circulating nucleosides to wild-type in hours for up to three weeks at 0.25 mg/kg. Subcutaneous dosing works if you add hyaluronidase.
Source preprint: mRNA-LNP therapy restores systemic nucleoside imbalance in a mitochon-drial DNA depletion syndrome
- biorxiv2026-08-14score 94OXPHOSmetabolismneurobiology
POLG occipital epilepsy is an immunometabolic lesion: OXPHOS collapse meets innate inflammation in visual cortex
In 12 post-mortem POLG-related epilepsy brains, occipital cortex (BA17) loses mitochondrial proteins and gains an innate-immune proteome, including OXPHOS-poor microglia. Control visual cortex is already richer in OXPHOS and interneuron proteins than frontal cortex — a baseline that may explain why status epilepticus detonates occipitally in this mitochondrial disease.
Source preprint: Neuroinflammation and metabolic dysfunction in POLG-related mitochondrial epilepsy
- biorxiv2026-09-07score 93OXPHOSstructural biologyassembly
Cryo-EM shows Complex III does not assemble the two protomers in parallel, and CIII2CIV is born during that assembly
The textbook stepwise, symmetric assembly of dimeric mitochondrial Complex III is wrong in the cryo-EM intermediates. Subunit incorporation can uncouple from folding (cytochrome c1), and after dimerization the two protomers do not mature in lockstep (intermembrane-space domain). Non-vertebrate supercomplex CIII2CIV forms on that same assembly path, which favors cooperative supercomplex birth over late docking of finished complexes.
Source preprint: Cryo-EM reveals the central steps of mitochondrial complex III assembly and the cooperative assembly of supercomplex CIII2CIV
- biorxiv2026-08-26score 93calcium signalingtherapeuticsapoptosis
NLRX1 is the CypD-independent handle on the mitochondrial permeability transition pore
Two chemically unrelated, brain-penetrant inhibitors of the mitochondrial permeability transition pore (mPTP) bind the mitochondrial NOD-like receptor NLRX1, and binding potency tracks pore blockade. Loss of NLRX1 raises the calcium threshold for pore opening in CRISPR-edited human cells and Nlrx1-knockout mouse tissue, independently of cyclophilin D (CypD); the oral lead GSK900 is active in an mPTP-sensitive neurological injury model.
Source preprint: NLRX1 is an essential, druggable regulator of mitochondrial permeability transition
- biorxiv2026-09-06score 92importproteostasisapoptosis
Raptinal does not punch mitochondria; it jams folding, then TIM23 import permeabilizes the organelle
Proteostasis failure can kill mitochondria without BAX and BAK. Raptinal, the textbook fast apoptotic, is shown here as a folding poison. Misfolded new proteins flood import, the outer membrane opens, and VBIT4 plus TIM23-PAM blockade stop that death without touching canonical BAX-BAK apoptosis. Import flux is the fuse between a broken cytosol and a leaky organelle.
Source preprint: Mitochondrial protein import couples proteostasis failure to mitochondrial permeabilization
- biorxiv2026-09-03score 92ironcontact sitesbioenergetics
Lysosomes hand Fe(II) to mitochondria at contact sites, skipping mitoferrins and the cytosol
The textbook says mitochondria drink ferrous iron from the cytosolic labile pool through MFRN transporters. Live structured-illumination microscopy here shows Fe(II) crossing mitochondria-lysosome contacts on a PPS39/TOMM22/SFXN1 path that bypasses that pool. SFXN1 knockdown drops mitochondrial Fe(II) even when you ignore its serine job. Lysosomes are not just storage. They are a direct iron dock.
Source preprint: A direct, MFRN-independent Fe(II) transfer pathway at mitochondria-lysosome contacts
- biorxiv2026-08-13score 92mtDNAOXPHOSmetabolism
Past 70% mtDNA heteroplasmy, cells need pyruvate carboxylase — or exogenous asparagine — to keep translating
Isogenic mtDNA-deletion lines show linear loss of respiration with heteroplasmy, but redox stress, ISR, and translation failure only after discrete thresholds (~50% and ~70%). Those late defects reverse with asparagine or pyruvate carboxylase overexpression. Respiration-deficient cells become asparagine auxotrophs when PC is low — and L-asparaginase shrinks a high-heteroplasmy, low-PC thyroid tumor model.
Source preprint: Respiration-Deficient Cells Require Pyruvate Carboxylase to Suppress Asparagine Auxotrophy
- biorxiv2026-09-17score 91OXPHOScardiologyAMPK
AMPK restores respiration in TMEM70 Complex V-deficient human cardiomyocytes without fixing ATP synthase
TMEM70 is the most common nuclear cause of mitochondrial ATP synthase (Complex V) deficiency, and the heart is where it hurts. In CRISPR-edited human induced pluripotent stem-cell cardiomyocytes, the organelle looks fine in the stem-cell state and then loses membrane potential, respiratory capacity, and structural discipline once the cells become heart muscle. Chronic AMP-activated protein kinase (AMPK) activation puts respiration and fatty-acid metabolism back and quiets pathological remodeling, even though Complex V itself stays broken.
Source preprint: AMPK reinforces mitochondrial metabolism and suppresses pathological remodeling in Complex V-deficient cardiomyocytes
- biorxiv2026-09-09score 91calciumbioenergeticscardiology
CGP7930 turns on the mitochondrial calcium uniporter via MICU1 and lifts mouse heart contraction
A 1,280-compound screen finds CGP7930 as a potent mitochondrial calcium-uniporter activator that needs MICU1 (not MICU2), docks at MICU1 Gln304/Val307, adds mitochondria-ER contacts, and raises cardiomyocyte bioenergetics and ventricular force. MCU-knockout hearts do not contract harder when you perfuse the compound.
Source preprint: High-throughput screen identifies a potent MCU activator boosting cardiac contractile bioenergetics
- biorxiv2026-09-03score 91cardiologymetabolismautophagy
Adult cardiomyocyte prohibitin knockout unleashes mTORC1, Warburg-like amino-acid synthesis, and fatal DCM
Delete the PHB1/2 complex in adult mouse cardiomyocytes and mTORC1 runs unrestrained. Glucose carbon swings toward de novo amino acids, mitochondrial calcium handling breaks, autophagy fails, the heart dilates, and the animals die within 12 weeks. mTORC1 inhibition eases remodeling only in females.
Source preprint: Cardiomyocyte prohibitin ablation reprograms cardiac metabolism revealing a pathogenic role for mTORC1 in dilated cardiomyopathy
- biorxiv2026-08-12score 91OXPHOSmetabolismredox biology
Clever-1 sits on AML mitochondria, feeds complex IV with lipoprotein lipid, and is a bexmarilimab-sensitive OXPHOS liability
Clever-1 is not only an immune scavenger receptor. In AML it localizes to mitochondria, associates with ATAD3, delivers lipoprotein-derived lipid, and supports complex IV assembly, cristae, and spare respiratory capacity. Antibody blockade (bexmarilimab) collapses that program, hardest in OXPHOS-high models and under lipid restriction.
Source preprint: Clever-1 blockade disrupts lipid metabolism and mitochondrial fitness in acute myeloid leukemia
- biorxiv2026-09-09score 90mitophagyParkinson diseaseimport
Vertebrate PINK1 needs TOM20 and its terminal extensions to keep the kinase domain folded
Human PINK1 has been a recombinant headache because vertebrates rewired how the kinase stays folded. Predicted TOM20 binding is mostly a vertebrate trick, coinciding with a rewritten N- and C-terminal extension interface. Insect PINK1 purifies active; vertebrate PINK1 does not, until you give it insect extensions or extra TOM20. A mostly human chimera then scores R152W as likely pathogenic.
Source preprint: Evolutionary analysis of PINK1 reveals key roles of the N- and C-terminal extensions and TOM20 in folding its kinase domain
- biorxiv2026-09-03score 90mitochondrial transferimmunologyislet
Beta cells hand mitochondria to islet macrophages, and the receivers turn on Arc and make more protein
Mice with beta-cell-only mitochondrial GFP show those organelles arriving in islet macrophages in vivo and in vitro. Diabetogenic stress does not change how often it happens. Macrophages that took the gift synthesize more protein and raise Arc; blocking actin dynamics stops the transfer. Islet homeostasis now includes organelle traffic, not only cytokines.
Source preprint: Mitochondrial transfer mediates metabolic communication between beta cells and islet macrophages
- biorxiv2026-09-01score 90Parkinson diseaseimportOXPHOS
VDAC1 sends DJ-1 into the matrix under stress; only matrix DJ-1 saves neuronal respiration
Endogenous DJ-1 binds VDAC1. Without VDAC1, stress-driven DJ-1 fails to reach the mitochondrial matrix. VDAC1-null neurons fragment, lose OXPHOS and ATP, mishandle ROS, and die more to MPP+. Matrix-targeted DJ-1, not outer-membrane DJ-1, restores basal, ATP-linked, and maximal respiration, shape, and survival. ATP-synthase inhibition itself recruits mitochondrial DJ-1.
Source preprint: VDAC1 regulates stress-associated matrix localization of DJ-1 to support mitochondrial homeostasis and neuronal survival
- medrxiv2026-08-25score 90mtDNAgeneticsmetabolism
251,512 biobank genomes already held mitochondrial DNA. This pipeline finally calls it.
A portable Mitoverse mtDNA-Server 2 Fusion workflow, run natively at Mount Sinai (54,151 whole-exome participants) and reimplemented under All of Us Workbench constraints (197,361 whole-genome participants), produced 12.9 million mitochondrial DNA variant observations across 251,512 people without new sequencing. The missing product was never the reads. It was a harmonized, heteroplasmy-aware call set that biobanks would actually ship.
Source preprint: A Scalable Framework for Harmonized mtDNA Analysis Across Diverse Biobanks
- biorxiv2026-09-07score 89cancerOXPHOSfusion
Triple-negative cells that survive radiation rebuild mitochondria through the short OPA1 isoform
After ionizing radiation, residual triple-negative breast-cancer cells swell their mitochondrial mass, cristae, oxidative phosphorylation, and metabolites, then largely revert when they regrow. The short OPA1 isoform rises in the residual state; OPA1 knockout erases the rewiring, and genetic or drug OPA1 blockade improves the radiation response.
Source preprint: Mitochondrial rewiring supports survival of triple negative breast cancer cells after ionizing radiation
- biorxiv2026-09-03score 89infectionfusionmtDNA
HSV-1 shreds mtDNA and OPA1 so mitochondria shrink to the nucleus and serve the virus
HSV-1 uses UL12.5 to erase mitochondrial DNA and the biogenesis factors PGC-1alpha and TFAM. Independently it activates OMA1 to cleave OPA1, drops MFN2, and down-modulates TIM23, so the network fragments and huddles perinuclearly. Fail to make those changes and the infection suffers. Mitophagy is still held off (abstract cuts there).
Source preprint: Herpes simplex virus 1 subverts the mitochondrial network to support the infection: A lesson on mitochondrial versatility
- biorxiv2026-08-20score 89cancerOXPHOSredox biology
HES1-low senescent CTCs keep OXPHOS and SOD1 — and those are the cells that regrow metastases
Senescence in circulating tumor cells is not one state. HES1-low senescent CTCs keep mitochondrial fitness, oxidative phosphorylation, and SOD1-dependent ROS detox, and they regrow tumors more efficiently than HES1-high cells. HES1 binds the Sod1 promoter and represses it; dual SOD1 inhibition plus ABT737 hits both residual pools in vivo.
Source preprint: The HES1-SOD1 Antagonism Shapes Senescence Heterogeneity and Impacts Metastatic Relapse of Circulating Tumor Cells
- biorxiv2026-09-17score 88OXPHOSagingAMPK
Complex I and Complex IV longevity in C. elegans use opposite retrograde paths, and metformin can tell them apart
Mild electron-transport-chain lesions extend Caenorhabditis elegans life, and the usual story treats mitohormesis as one program. Knock down Complex I (nuo-6) and lifespan needs the mitochondrial unfolded protein response factor ATFS-1 and ignores the AMP-activated protein kinase (AMPK) ortholog AAK-2. Knock down Complex IV (cco-1) and the dependencies flip. Metformin, a Complex I inhibitor and AMPK activator, then suppresses one longevity genotype and leans toward helping the other.
Source preprint: Divergent Retrograde Signaling Pathways Coordinate Longevity and Metformin Responses in Complex I and Complex IV Deficient C. elegans
- biorxiv2026-09-08score 88OXPHOSimmunologyinfection
As tuberculosis becomes chronic, myeloid cells lose electron-transport-chain transcripts and then lose control of the bacillus
Single-cell RNA-seq of mouse tuberculosis shows a coordinated collapse of mitochondrial electron-transport-chain genes across myeloid subsets as disease chronicles. Knocking down macrophage Complex I (Ndufs4) drops MHC-II, scrambles inflammatory transcription, and lets Mycobacterium tuberculosis replicate. Household contacts who convert an interferon-gamma release assay carry almost the same respiratory-remodeling program.
Source preprint: Loss of Mitochondrial Respiratory Capacity Reshapes Myeloid Cell Function during Mycobacterium tuberculosis infection
- biorxiv2026-09-06score 88bioenergeticscardiolipinOXPHOS
Cardiolipin’s minus-two charge digs a 14.3 kT well that keeps protons on the inner membrane
A constrained two-dimensional continuum model, trained on DOPG fluorescence kinetics and real buffer-consumption rates, splits the interfacial proton trap into a 5.7 kT water barrier plus a 4.3 kT monovalent-lipid electrostatics term. Cardiolipin’s −2e charge then predicts a 14.3 kT well that holds protons 1–2 nm from the membrane, kills vertical leak, and accelerates lateral delivery to ATP synthase.
Source preprint: Nanoscale spatial confinement of proton flux by cardiolipin drives high-speed lateral proton transport in mitochondria
- biorxiv2026-09-04score 88fusioncardiologymtDNA
A rare de novo OPA1 Pro188Leu fragmentates cardiomyocyte mitochondria and tanks ATP and respiration
Whole-exome sequencing of dilated-cardiomyopathy cases finds a rare de novo OPA1 c.563C>T (p.Pro188Leu). Models predict a 3.5 angstrom distortion and easier OMA1 access, hence more cleavage and fission. In H9C2 cells the mutant lowers OPA1 protein, fragments mitochondria, drops membrane potential, ATP, and oxygen consumption, raises cytosolic calcium and ROS, cuts mtDNA copy number, and turns on intrinsic apoptosis marks.
Source preprint: Implication of a rare variant in OPA1 in Cardiac Pathophysiology: From Cristae Remodelling to Contractile Dysfunction
- biorxiv2026-08-19score 88mitochondrial dynamicsmitophagyredox biology
MICOS Chchd3 loss breaks the fly heart through mitophagy, ROS, and ER stress — not ROS alone
Cardiac knockdown of the MICOS subunit Chchd3 in Drosophila raises ROS and ER stress and genetically depends on Pink1/parkin mitophagy. Catalase overexpression fully normalizes ROS but only partly restores contractility; Xbp1 does the same for ER stress. Catalase knockdown raises ROS without hurting the heart. Congenital-heart-disease candidate MICOS failure is a multi-stress organelle problem, not a single oxidant dump.
Source preprint: Deficiency in MICOS component Chchd3 Compromises Drosophila Heart Function via mitophagy, ROS and ER Stress
- biorxiv2026-08-15score 88OXPHOSredox biologyapoptosis
IVF and vitrification depolarize the blastocyst mitochondrion; the adult mouse heart still shows the bioenergetic scar
Mouse IVF and embryo vitrification are separable mitochondrial injuries. Both lower blastocyst ΔΨm and glutathione; ROS is highest in vitrified IVF embryos. After transfer, adult left-ventricular mitochondria have less OXPHOS capacity, more H2O2 per oxygen, altered OXPHOS subunit abundance, and reduced complex I, III and IV activity. The organelle is a plausible lasting carrier of ART cardiovascular risk.
Source preprint: In vitro fertilisation and vitrification disrupt embryo mitochondrial function and redox balance that persists into adulthood in mice
- biorxiv2026-08-13score 88neurobiologycalcium signalingOXPHOS
LRRK2 astrocytes extrude calcium slowly; PRKN astrocytes run hotter OXPHOS; both fragment mitochondria
Parkinson’s hiPSC astrocytes are not a single mitochondrial phenotype. LRRK2 G2019S cells hold less cytosolic calcium and extrude it more slowly after ATP. PRKN mutant astrocytes run a more oxidative bioenergetic program than LRRK2 mutants. Both genotypes fragment mitochondria, park them at the periphery, alter DRP1 phosphorylation, and lose respiratory-complex protein.
Source preprint: Mitochondrial Metabolism and Calcium Handling in Parkinson's Disease hiPSC-derived Astrocytes
- biorxiv2026-09-08score 87neurobiologyfusionglia
Low testosterone opens the nucleus-accumbens blood-brain barrier by remodeling astrocyte mitochondria
In outbred male rats, low testosterone is not just a mood correlate. It raises anxiety by loosening the nucleus accumbens blood-brain barrier, and the physical failure is astrocytic: fewer endfeet, disordered endfoot mitochondria, fewer mitochondria-endoplasmic-reticulum contacts, less mitofusin 2. Restore testosterone, or put Mfn2 back in accumbens astrocytes, and anxiety falls.
Source preprint: Low testosterone promotes anxiety through astrocytic mitochondrial remodelling at the nucleus accumbens blood-brain barrier
- biorxiv2026-09-07score 87agingmusclecardiology
Blocking miR-128-3p turns mitochondrial programs back on in aged, infarcted, and dystrophic muscle
The positively selected miR-128-1 locus tracks human grip, lung, and cardiometabolic traits. Antisense inhibition of miR-128-3p restores aged mouse muscle, helps infarcted hearts, and eases Duchenne pathology in mouse and pig, while a conserved transcriptome lights mitochondrial programs and dims inflammation and fibrosis, like a longevity intervention.
Source preprint: A positively selected microRNA controls a reversible aging program in striated muscle
- biorxiv2026-09-02score 87mtRNAinnate immunityapoptosis
mtRNA leaves through BAX/BAK and VDAC1, then m6A decides how long RIG-I can see it
Abt-373 and VSV push mitochondrial RNA (and mtDNA) into the cytosol through BAX/BAK and VDAC1. In A549 cells that RNA lights RIG-I, MDA5, TLR3/7/8, and PKR. The RNA carries m6A; the methylation machinery sets how long it stays cytosolic and how it binds RIG-I, which sets the inflammatory gain.
Source preprint: The mitochondrial RNA extrusion-induced innate immunity is regulated by N6-methyladenosine machinery
- biorxiv2026-08-12score 87metabolismOXPHOSmitochondrial dynamics
DGAT1 lipid droplets shield nurse-cell mitochondria — without them, fatty acids flood in and oogenesis arrests
Drosophila nurse-cell mitochondria oxidize fatty acids in a stage-dependent way, peaking at mid-oogenesis, and they draw that fuel from ATGL-released lipid-droplet triglyceride. Blocking droplet formation with DGAT1 mutants dumps fatty acids into mitochondria, collapses function, and arrests the follicle. Restricting fatty-acid influx into the follicle or into mitochondria rescues. Lipid droplets are a mitochondrial buffer, not just an embryonic larder.
Source preprint: Monitoring fatty acid trafficking during Drosophila melanogaster oogenesis reveals a role for the triglyceride synthase DGAT1 in protecting mitochondrial integrity
- biorxiv2026-08-11score 87cancertherapeuticsOXPHOS
ClpP agonist TR-107 collapses ACC respiration at nanomolar doses and synergizes with IGF-1R blockade
TR-107, a selective agonist of the mitochondrial protease ClpP, kills adrenocortical carcinoma cells and patient-derived organoids at nanomolar concentrations by wrecking oxidative phosphorylation. Oxygen consumption falls, ROS rise, ferroptosis-rheostat proteins come up, and the compound is not an ABCB1 substrate. Combined with IGF-1R inhibitors, the kill is synergistic.
Source preprint: TR-107, a novel mitochondrial ClpP agonist, induces robust antitumor activity against preclinical models of adrenocortical carcinoma
- biorxiv2026-09-09score 86OXPHOSredox biologyiron
Rotenone Complex I block raises mitochondrial iron through ROS, then iron feeds the ROS back
In differentiated dopaminergic neurons, rotenone inhibition of mitochondrial Complex I is enough to mis-place iron: mitochondria and the whole cell gain iron while the cytosol loses labile iron. Reactive oxygen species (ROS) sit in the middle of that shift, and iron then amplifies the same ROS, a loop with a direct line to Parkinson disease and other iron-loading mitochondrial disorders.
Source preprint: Reactive Oxygen Species Generation Drives Iron Accumulation by Rotenone-Mediated Inhibition of Mitochondrial Complex I in Dopaminergic Neurons
- biorxiv2026-09-07score 86mitophagyERubiquitin
ER ligase Gp78 builds DFCP1 omegasomes and chews mitochondrial proteins there, without PINK1 or Parkin
Mitophagy is not only a Parkin coat on a damaged mitochondrion. The ER-resident E3 ligase Gp78 sits on DFCP1-positive omegasomes, needs its RING and the BAG6-UBL4A-USP13 module, and drives outer-membrane loss (TOMM20-negative intermediates) while mitochondria are still in one piece. PINK1 and Parkin are dispensable.
Source preprint: The Gp78 ubiquitin E3 ligase drives mitophagy by regulating omegasome formation
- biorxiv2026-09-03score 86mitochondrial dynamicsredox biologymetabolism
Losing ELM1B freezes moss mitochondrial fission, oxidizes the matrix, and weakens stress tolerance
In the moss Physcomitrium patens, mito-paraquat oxidizes glutathione in mitochondria, cytosol, and chloroplasts, elongates mitochondria within hours, and raises a heterogeneous matrix EOS-red signal that the authors propose as a protein-damage mark. Genetic loss of PpELM1B (ELONGATED MITOCHONDRIA 1B) locks that elongated state, shifts matrix glutathione more oxidized, increases EOS red, slows growth and respiration, and makes plants more sensitive to oxidative stress, even though matrix mixing still occurs at the same slow, days-long rate as in wild type.
Source preprint: Loss of ELM1B impairs mitochondrial fission, matrix redox state and stress tolerance in Physcomitrium patens
- biorxiv2026-09-03score 86therapeuticsbioenergeticslung
Sobetirome eases lung fibrosis by restoring mitochondrial homeostasis through THRB-PPARGC1A
The thyroid-hormone-receptor-beta agonist sobetirome, given in the belly or the airway, cuts bleomycin lung fibrosis in mice without obvious toxicity. It restores mitochondrial homeostasis via THRB-PPARGC1A (PGC-1alpha), saves alveolar type II cells from apoptosis, and kills stubborn IPF fibroblasts. Delete Ppargc1a in epithelium or fibroblasts and the drug fails. Human IPF tissue transcription moves back, including COL1A1 and friends.
Source preprint: Sobetirome, a thyroid hormone receptor beta agonist, is a potential therapeutic agent for pulmonary fibrosis
- biorxiv2026-08-26score 86mitochondrial dynamicsneurobiologygenetics
TRAK2 unlocks kinesin-1 at coiled-coil 4 by breaking a hidden CC1-CC4 latch
The mitochondrial adaptor TRAK2 binds the kinesin-1 heavy chain KIF5C at the CC4 cargo platform in a defined 2:2 complex that is required to recruit KIF5C to mitochondria. A previously unrecognized intramolecular latch between KIF5C coiled-coil 1 and coiled-coil 4 holds the motor off; TRAK2 and the light chain KLC1 release that latch by different routes, so holoenzyme composition decides whether mitochondria can hire the motor.
Source preprint: Kinesin-1 holoenzyme assembly coordinates cargo-adaptor recognition with heavy-chain autoinhibition
- biorxiv2026-08-20score 86immunologymtDNAcomputational
Ancient human mtDNA encrypts antimicrobial peptides; 14 kill bacteria and one works in mouse skin
Mining 2,025 ancient human mitochondrial genomes produced 65 encrypted peptide candidates the authors call mitochondrins. Thirty-eight were synthesized; 14 killed clinically relevant Gram-negative and Gram-positive bacteria. Activity tracked hydrophobic-cationic patterning, not length or charge alone, and one peptide reduced bacterial burden in a murine skin-abscess model.
Source preprint: Ancient human mitochondrial genomes encode antimicrobial peptides
- biorxiv2026-08-20score 86immunologymitochondrial dynamicstherapeutics
Gelsolin keeps macrophage mitochondria intact during Legionella infection and buys survival without changing bacterial load
Gelsolin-knockout mice die faster from severe Legionella pneumophila pneumonia despite unchanged lung bacterial loads. Macrophages overproduce CXCL1/KC, lungs accumulate neutrophils and apoptotic cells, gelsolin-null neutrophils make fewer NETs and lose mitochondrial capacity, and infected macrophages lose mitochondrial network morphology and respiration. Recombinant gelsolin extends survival, reduces lung pathology, and calms the macrophage inflammatory signature. Host mitochondrial integrity, not CFU, is the survival variable.
Source preprint: Gelsolin protects mitochondria and regulates inflammation during Legionella pneumophila infection
- biorxiv2026-08-17score 86OXPHOSredox biologymetabolism
APX2014 rewires mitochondrial cysteine, phospho, and acetyl marks in minutes — the proteome has not moved yet
A 30–120 minute pulse of the Ref-1/APE1 redox inhibitor APX2014 remakes PTMs, not protein abundance, in PDAC cells. Cysteine oxidation leads; phosphorylation and lysine acetylation follow; the earliest enriched processes are mitochondrial translation, electron transport, TCA metabolism, and mitochondrial redox homeostasis, matching a functional drop in TCA-substrate use.
Source preprint: Integrated Post-Translational Modification (PTM) Proteomics Reveals Early Redox and Mitochondrial Remodeling Following Ref-1 Inhibition in Pancreatic Cancer
- biorxiv2026-09-09score 85redox biologyneurobiologymetabolism
Female hypothalamic microglia resist early obesity with a redox-and-mitochondria program until mTORC1 breaks it
In females, not males, hypothalamic microglia answer a high-fat diet with more antioxidant capacity and a remodeled mitochondrial network, which delays early weight gain. Microglial mTORC1 later wrecks those mitochondria and ends the grace period. Sex-specific obesity risk has an organelle switch in a brain-resident immune cell.
Source preprint: A Female-Specific Microglial Redox Program Gates Susceptibility to Obesity
- biorxiv2026-09-06score 85cancerproteostasisone-carbon
Mitochondrial HSP60 (HSPD1) holds MYCN up in amplified neuroblastoma
Deplete HSPD1 (HSP60) in MYCN-amplified neuroblastoma and mitochondrial translation falls, MYCN itself falls, and tumors shrink in vitro and in vivo. HSPD1 RNA and protein track MYCN in tumors. The chaperone is not just a MYCN slave.
Source preprint: HSPD1 promotes neuroblastoma by augmenting MYCN expression
- biorxiv2026-08-17score 85metabolismtherapeuticscancer
Sertraline plus carfilzomib starves SSP-active T-cell tumors of cholesterol flux and mitochondrial respiration
In T-cell acute lymphoblastic leukemia (T-ALL) and peripheral T-cell lymphoma (PTCL) cells that run the serine/glycine synthesis pathway (SSP), the antidepressant sertraline and the proteasome inhibitor carfilzomib are synergistic because they pull cholesterol in opposite directions and together collapse mitochondrial respiration. The pair works in an aggressive MYCN PTCL mouse model and remakes the immune microenvironment, while largely sparing SSP-inactive tumor cells and healthy blood cells.
Source preprint: Sertraline and Carfilzomib Synergize to Target T-cell Malignancies with Serine/Glycine synthesis activity via Cholesterol Dysregulation, Cellular Stress and Immune Modulation
- biorxiv2026-09-09score 84fissionfusionstem cells
Light-dark cycles tune Drp1 on ovarian stem-cell mitochondria so a protein-rich diet can make eggs
Drosophila ovarian germline stem cells only convert a protein-rich meal into eggs if the light-dark clock has parked the fission protein Drp1 on mitochondria in the right pattern. Cryptochrome sets the rhythm, Opa1 can reverse it, threonine is the amino-acid cue, and follicle stem cells want a different Drp1 tune. The same priming undoes a diabetes-like brake on egg development.
Source preprint: Interaction of light-dark and dietary cues prime Drosophila ovarian stem cell properties by precisely tuning Drp1 recruitment and organization on mitochondria
- biorxiv2026-09-03score 84OXPHOSinfectionstructural biology
Toxoplasma crosslinking finds a divergent ATP-synthase alpha subunit the parasite cannot live without
A proteome-wide XL-MS map of Toxoplasma (29,624 crosslinked pairs, 2,859 interactions) plus structure models turns up new essential-complex members, including an apicomplexan-specific ATP-synthase alpha in a structurally distinct subcomplex required for fitness. Core mitochondrial machinery diversified, and that is a drug-shaped hole.
Source preprint: Proteome-wide crosslinking mass spectrometry reveals novel components of essential complexes in Toxoplasma
- medrxiv2026-09-02score 84mitophagytherapeuticsaging
Pemafibrate restores TFEB-driven mitophagy and flattens FEV1 decline versus older fibrates
Chronic obstructive pulmonary disease (COPD) airway epithelium is short on transcription factor EB (TFEB). Pemafibrate, a selective peroxisome proliferator-activated receptor alpha agonist already used for lipids, restores autophagy and mitophagy flux plus lysosomal acidification in smoke-exposed human bronchial epithelial cells, limits emphysema and lung stiffness in chronically smoked mice, and in a retrospective clinic cohort associates with slower forced expiratory volume in 1 second (FEV1) decline than bezafibrate or fenofibrate.
Source preprint: Senotherapeutic role of pemafibrate through autophagy/mitophagy regulation in chronic obstructive pulmonary disease
- biorxiv2026-08-19score 84metabolismOXPHOScancer
GALC knockout loads melanoma mitochondria with ceramide and sphingomyelin and throttles respiration without wrecking structure
Knocking out the lysosomal sphingolipid enzyme β-galactosylceramidase (GALC) in A2058 human melanoma cells remakes the mitochondrial sphingolipid profile and produces bioenergetic insufficiency without major mitochondrial structural change. The authors attribute the energy failure to ceramide- and sphingomyelin-driven impairment of respiratory-chain function. GALC is a lipid-to-OXPHOS lever in this line, consistent with prior work that treated GALC as pro-oncogenic.
Source preprint: Impact of the sphingolipid metabolizing enzyme β-galactosylceramidase on mitochondrial sphingolipid profile and energetic metabolism in human melanoma cells
- medrxiv2026-08-11score 84mitochondrial dynamicsmitophagycalcium signaling
De novo MFN2 N311S distorts the GTPase fold, weakens Parkin binding, and fragments cardiomyoblast mitochondria
Whole-exome sequencing of 15 DCM cases found a rare de novo MFN2 c.932A>G (p.N311S) GTPase-domain variant. Structural modeling predicts a large conformational hit (RMSD 8.95 Å) and weaker MFN2–PRKN docking. In stable H9c2 lines the mutant protein is scarce, mitochondria cluster and fragment, ΔΨm/ATP/OCR fall, cytosolic Ca2+ and ROS rise, and hypertrophic PI3K/AKT/mTOR plus Myh6/Nppa/Nfatc programs turn on.
Source preprint: A loss-of-function mutation in the GTPase domain of MFN2 , perverting mitochondrial dynamics, is associated with dilated cardiomyopathy
- biorxiv2026-08-10score 84mitophagyautophagystructural biology
Rubicon clamps PI3KC3-C2 via a UVRAG-shaped BECN1 BARA pose; breaking that interface restores mitophagy
Cryo-electron microscopy of the class III phosphatidylinositol 3-kinase complex II (PI3KC3-C2) bound to Rubicon’s PI3K-binding domain shows why Rubicon inhibits the UVRAG-containing C2 complex and not the ATG14-containing C1 complex. Rubicon binds only the BECN1 BARA domain, a subunit shared by C1 and C2. Selectivity comes from a UVRAG-induced BARA conformation, not from a direct UVRAG contact or ATG14 antagonism. Mutations that break the interface raise mitophagy in human epithelial cells to Rubicon-knockout levels and restore lysosomal flux in Rubicon-overexpressing hippocampal neurons. PI3KC3-C2 suppression fully accounts for Rubicon’s autophagy and endolysosome brake.
Source preprint: Structural basis for the selective inhibition of the PI3KC3-C2 complex by Rubicon in endolysosome maturation and mitophagy
- biorxiv2026-09-07score 83metabolismcytoskeletoninsulin
Losing PTPRF rewires actin, raises mitochondrial respiration in hepatocytes, and frees insulin granules in beta cells
The receptor phosphatase PTPRF is a nutrient-stress checkpoint: spliced XBP1 turns it down, actin filaments reorganize, hepatocytes shift toward oxidative mitochondrial metabolism and less steatosis, and obese beta cells release more insulin. Cytoskeleton and mitochondria are on the same adaptive circuit, not parallel chapters.
Source preprint: PTPRF is a stress-responsive cytoskeletal checkpoint that coordinates metabolic adaptation in hepatocytes and β cells
- biorxiv2026-08-19score 83apoptosisredox biologyimmunology
Isoflurane depolarizes CD4 T-cell mitochondria and opens a reversible ROS–p38–caspase death path; propofol does not
In CD4+ helper T cells from women undergoing breast-cancer surgery (n=15 per anesthetic) and in Jurkat cells, clinically relevant isoflurane triggers mitochondrial depolarization, ROS, DNA damage, and caspase-3/7 apoptosis through p38 MAPK. Caspase inhibition, N-acetyl cysteine, and a p38 inhibitor all rescue. Propofol preserves mitochondrial integrity, lowers oxidative stress, and supports higher proliferation. The injury is transient: patients recover postoperatively, and Jurkat cells recover within 24–48 hours of washout.
Source preprint: Differential Impact of Isoflurane and Propofol on Apoptotic Regulation of Helper T cells
- biorxiv2026-08-19score 83OXPHOSneurobiologyimmunology
In Ndufs4 Leigh mice, hypoxia sits upstream of immune attack; stopping it detonates disease
In the Ndufs4 knockout mouse model of Leigh syndrome, brainstem immune profiling and timed therapy cessations split two preclinical interventions. Pexidartinib and rapamycin leave benefits that persist after the drugs stop. Stopping chronic mild hypoxia (11% oxygen) triggers rapid disease onset and faster progression. Pre-onset animals lack an inflammatory signature; wiping out leukocytes erases the molecular disease signature, and macrophages/monocytes appear to drive pathology. Hypoxia looks upstream of immune activation, which is a translational warning: hypoxia is not a durable disease-modifying holiday the way immune targeting can be.
Source preprint: Hypoxia versus immune depletion - immune profiling and treatment cessation provide mechanistic insights and considerations for translation in Leigh syndrome
- medrxiv2026-09-08score 82mtDNAophthalmologybiomarkers
Lower blood mitochondrial DNA copy number tracks faster visual-field loss in open-angle glaucoma
In 200 people with primary open-angle glaucoma followed for about 11 years, fewer mitochondrial DNA copies in blood leukocytes associate with a steeper slide in visual-field mean deviation. The link is strongest when peak intraocular pressure is not the obvious villain, which makes systemic mtDNA copy number a candidate reserve marker, not a pressure surrogate.
Source preprint: Mitochondrial DNA Copy Number Is Associated With Visual Field Progression in Primary Open-Angle Glaucoma
- biorxiv2026-09-03score 82mtDNAdevelopmentoocyte
The mouse oocyte Balbiani body comes back in growing follicles to keep selecting mitochondria
The mouse Balbiani body, a mitochondria-rich oocyte cloud thought to pause after primordial-follicle birth, reassembles around one microtubule-organizing center during follicle growth, still packed with mitochondria, Golgi, ER, and endosomes. It later disperses as the MTOC and nucleus are moved by microtubule-versus-actin forces. Quality control of organelles is not a one-shot zygotene event.
Source preprint: The mouse oocyte Balbiani body reassembles in growing follicles to continue organelle selection and upon dispersal influences nuclear position
- biorxiv2026-08-31score 82Parkinson diseasemitophagytherapeutics
Simvastatin, via RhoA, fixes mitochondrial and lysosomal PD phenotypes in patient iPSC dopamine neurons
Simvastatin and the RhoA blocker rhosin rescue neurites, mitochondria, lysosomes, cytokines, and death in familial-PD and isogenic PARK2-null iPSC dopamine neurons. RhoA inhibition moves mitophagy and autophagy markers toward better turnover. A 32-line RhoA-activity screen is started (abstract cuts off).
Source preprint: Simvastatin attenuates disease phenotypes in human induced pluripotent stem cell models of familial Parkinson’s disease through RhoA inhibition
- biorxiv2026-08-20score 82OXPHOSthermogenesisbioenergetics
Human UCP1 uncouples like mouse UCP1 but prefers ATP over GDP, tracing in part to F88S
Human and mouse uncoupling protein 1 (UCP1), expressed with adeno-associated virus in mouse liver and assayed in isolated liver mitochondria, both cause marked innate uncoupling without added fatty acids. Mouse UCP1 keeps classical GDP inhibition and oleate reactivation. Human UCP1 is only weakly GDP-inhibited, is strongly fatty-acid responsive, and is potently inhibited by ATP (apparent IC50 about 0.4 mM versus about 1.4 mM for GDP). Molecular dynamics point to a persistent GDP–F88 contact in mouse UCP1 that is missing at S88 in human UCP1.
Source preprint: Differential Nucleotide Inhibition Profile of Mouse and Human UCP1 Expressed in Liver Mitochondria Is Associated with an F88S Mutation
- biorxiv2026-08-13score 82metabolismcardiologylipid
2-Hydroxyglutarate parks fatty acids in triglycerides and away from mitochondria and lipotoxic membranes
Both D- and L-2-hydroxyglutarate push fatty acids into triglyceride droplets and away from phospholipid synthesis, mitochondrial oxidation, and lipotoxic intermediates in primary human cardiac and vascular cells. L2HG is more potent despite lower accumulation: it raises DGAT-dependent TG synthesis, slows TG turnover, and constrains the ethanolamine Kennedy branch, depleting phosphatidylethanolamine. FAO, long-chain acylcarnitines, and lipid peroxidation fall, independent of pseudohypoxic transcription. In mice L2HG causes hypertriglyceridemia, remakes cardiac TG acyl chains, and limits ischemia-induced cardiac acylcarnitine buildup, matching a human 2HG–triglyceride association. 2HG decides how fat is allocated, not only whether it is burned.
Source preprint: 2-Hydroxyglutarate Redirects Fatty Acid Partitioning to Mitigate Lipotoxic Stress and Preserve Metabolic Fuel
- biorxiv2026-09-06score 81mtRNARNA decaystructural biology
SUV3 N-terminus docks PNPase S1 domain to build the human mitochondrial RNA degradosome
Processive mitochondrial RNA turnover is a PNPase-SUV3 machine. This paper names the minimum parts and, with crosslinking mass spectrometry, parks the SUV3 N-terminal domain against the PNPase S1 domain.
Source preprint: Molecular architecture and assembly of the human RNA Degradosome
- biorxiv2026-09-03score 81computationalmetabolismOXPHOS
Underpredicted mitochondrial ADP/ATP carrier kcat values, not leaderboard scores, break yeast growth models
Six machine-learning predictors of enzyme turnover number (kcat) are only moderately accurate on a BRENDA-derived set and collapse to R-squared of 0.20 or lower on EnzyExtract, where training-set overlap is thinner. When those predicted kcat values parameterize enzyme-constrained genome-scale models of Saccharomyces cerevisiae, benchmark rank does not predict growth accuracy. The failure localizes to high-leverage mitochondrial ADP/ATP carrier turnover numbers: underpredict them and the model chokes adenine nucleotide exchange and invents a cytosolic ATP shortage.
Source preprint: Beyond benchmark accuracy: machine-learning turnover-number predictors require system-level validation
- biorxiv2026-08-21score 81computationalgeneticsmtDNA
Plant mitochondria keep a compact AOX–NAC stress module; human disease genes pile onto an expanded ISR–mtDNA network
An Arabidopsis-versus-human in silico comparison finds the same mitochondrial stress logic in both kingdoms, but not the same architecture. Plants organize alternative respiration and retrograde signaling as a compact AOX–NAC module. Humans expand integrated-stress-response and mtDNA-maintenance neighborhoods — and those expanded modules are the ones enriched for mitochondrial disease genes.
Source preprint: From Plants to Patients: Mitochondrial Stress Signaling as a Systems Framework for Human Disease Vulnerability
- biorxiv2026-08-17score 81protein importquality controlproteostasis
Cytosolic presequence cleavage stabilizes stranded mitochondrial precursors and skips the proteasome alarm
Mitochondrial presequences are not only address labels. When a cytosol-targeted mitochondrial processing peptidase (cytoMPP) cleaves them before import, many mature proteins persist in the cytosol instead of being ubiquitinated, the proteasome is not induced, and the cell mounts a heat-shock response while failing to sequester precursors. That is a different alarm from other import-block models, and it implies the presequence itself is a cytosolic quality-control element.
Source preprint: Presequences of non-imported mitochondrial proteins serve as quality control elements in the cytosol
- biorxiv2026-08-17score 81metabolismredox biologyTCA cycle
Chlamydomonas NADK2 parks in mitochondria in the dark; without it the TCA cycle and heterotrophy fail
In Chlamydomonas reinhardtii, NADK2 is dual-targeted: mostly chloroplast in the light or on mixotrophy, increasingly mitochondrial in the dark on acetate. nadk2 mutants cannot make enough mitochondrial NADP(H), so the TCA cycle stalls and heterotrophic growth collapses. In the light, chloroplast NADK1 covers energy needs and acetate is rerouted through the glyoxylate shunt, bypassing TCA and cutting mitochondrial ROS. NAD kinase localization is plastic, and bypass metabolism is how the mutant survives daylight.
Source preprint: Dual-targeted NADK2 Links Mitochondrial Redox Homeostasis to Carbon Partitioning and Heterotrophic Growth in Chlamydomonas reinhardtii
- biorxiv2026-09-16score 80infectionmalariabioenergetics
Nutrient stress pushes Plasmodium falciparum into a pre-existing latent state that keeps mitochondria on
Artemisinin kills most Plasmodium falciparum malaria parasites and leaves a few that later recrudesce. Mild nutrient deprivation raises entry into a latent early-trophozoite state two- to three-fold after dihydroartemisinin, and that frequency tracks long-term recovery. The same transcriptional signature is already present, rare, in untreated cultures. Latent parasites throttle growth programs but selectively keep mitochondrial functions, redox control, nutrient uptake, lipid metabolism, and invasion kit.
Source preprint: Environmental stress promotes entry into a pre-existing latent state in Plasmodium falciparum
- biorxiv2026-09-09score 80mtRNARNA editingevolution
One diplonemid PPR-DYW protein, plus a PolX-like partner, edits more than 100 mitochondrial RNA sites
Diplonema papillatum concentrates C-to-U and A-to-I mitochondrial RNA editing into a two-protein core (PPRD1 and DAPX1) instead of the plant-style army of site-specific pentatricopeptide-repeat DYW deaminases. That is a different architecture for the same organelle problem: how to recode mitochondrial transcripts accurately at scale.
Source preprint: A microeukaryotic PPR-DYW protein supports multisite C- and A-deamination RNA editing
- biorxiv2026-09-05score 80metabolismnephrologyproteomics
Diabetic proximal tubule turns mitochondrial programs up; glomeruli just lose oxidative capacity
Deep visual proteomics of streptozotocin diabetic kidney splits two organelles’ fates. Proximal tubule loses proteostasis and structure and compensates with mitochondrial and lipid metabolism. Glomeruli lose oxidative metabolic capacity and do not compensate. Fourteen of the top twenty tubule candidates, including mitochondrial LARS2, move the same way in human CKD tubulointerstitium.
Source preprint: Deep visual proteomics reveals distinct proximal tubular and glomerular injury programs in experimental diabetic kidney disease
- medrxiv2026-09-03score 80Parkinson diseasemitophagygenetics
Indian early-onset Parkinson genetics pile onto mitochondrial organization and autophagy
In 668 young-onset Indian Parkinson cases (mean onset 39.4), half carry a reportable P/LP variant or VUS. Projected onto pathways, mitochondrial organization (73.5%), autophagy (67.9%), and synaptic-vesicle transport (59.8%) dominate. PRKN is the top P/LP gene. Ancestry-specific convergence still lands on the organelle.
Source preprint: From genes to pathways: genetic convergence in early-onset Parkinson’s disease in India
- biorxiv2026-08-21score 80mtDNAlineage tracingheteroplasmy
mtDNA mutations below 10% heteroplasmy double clonal assignment in barcoded blood cells
Somatic mitochondrial DNA mutations are used as natural single-cell barcodes, but most lineage papers keep only high-heteroplasmy variants. In lentivirally barcoded human hematopoietic cells, after molecule-level error filtering, calls below 10% per-cell heteroplasmy make up about half of lineage-informative mutations. Keeping the full heteroplasmy spectrum roughly doubles the clonal-assignment area under the precision-recall curve versus a greater-than-10% cutoff, and single-molecule-supported calls help when they are retained as a class.
Source preprint: Low-heteroplasmy mitochondrial DNA mutations improve clonal reconstruction of human cells
- biorxiv2026-08-19score 80bioenergeticscardiolipinOXPHOS
Cardiolipin raises surface proton activity fourfold and supports traveling H+ fronts on membranes
Cardiolipin, the dianionic inner-mitochondrial-membrane lipid, concentrates protons at the membrane surface. On giant planar phosphatidylcholine membranes, 20% cardiolipin enrichment raises surface H+ activity about fourfold, measured with fluorescein-DHPE. Both PC and cardiolipin membranes show non-Gaussian H+ profiles from a point source and support reversible acidification fronts that travel at constant speed between high- and low-pH states. A reaction-diffusion model attributes the fronts to autocatalytic (de)protonation of the surface. In mitochondria, the authors argue, such fronts would make cardiolipin-rich inner-membrane domains a higher-H+ low-pH state, potentially feeding the respiratory chain on one leaflet and ATP synthase on the other.
Source preprint: Cardiolipin increases the peak of reversible traveling H+ fronts at the membrane surface
- biorxiv2026-08-17score 80OXPHOSmetabolismcardiology
Losing FAHD1 stalls Complex II, derails the myosin switch, and hypertrophies maturing cardiomyocytes
The mitochondrial oxaloacetate decarboxylase FAHD1 is not a biochemical footnote. Germline Fahd1 knockout mice lose Complex II respiration and pyruvate, slide toward glycolysis and anabolic biosynthesis, fail the fetal-to-adult myosin switch, and develop left-ventricular systolic dysfunction with cardiomyocyte hypertrophy. That makes FAHD1 a gatekeeper of postnatal cardiac mitochondrial maturation.
Source preprint: A novel role for Oxaloacetate Decarboxylase FAHD1 in cardiomyocyte maturation
- biorxiv2026-08-17score 80protein importquality controlOXPHOS
Mitochondrial import stress dumps hydrophobic OXPHOS proteins at the ER for MARCHF6-led quality control
When mitochondrial import fails, hydrophobic oxidative phosphorylation (OXPHOS) proteins reroute to the endoplasmic reticulum (ER). Proximity proteomics, a split-fluorescence reporter, and genome-wide CRISPR show they then split into stable ER residents versus clients of ER-associated degradation (ERAD), with the ubiquitin ligase MARCHF6 as a central, partly redundant ligase. The ER is therefore a holding-and-disposal organelle for mistargeted mitochondrial proteins.
Source preprint: Selective quality control of mistargeted mitochondrial proteins at the endoplasmic reticulum
- biorxiv2026-08-17score 80immunologyOXPHOSmetabolism
HIF-1α makes intestinal RORγt+ Tregs mitochondrially sloppy and inflammatory
Hypoxia-inducible factor 1-alpha (HIF-1α) is a context-dependent checkpoint in intestinal RORγt-positive regulatory T cells. Deleting Hif1a in RORγt-expressing cells protects mice in acute dextran sulfate sodium (DSS) colitis, T-cell-transfer colitis, and azoxymethane/DSS colitis-associated cancer. Protection can travel with the Treg genotype alone. Those Tregs make more IL-10, less IL-17A and IFN-γ, suppress better, carry fewer dysfunctional and mitochondrial-ROS-high mitochondria, favor fusion-associated transcription, and show higher basal and maximal oxygen consumption and reserve capacity.
Source preprint: HIF-1α integrates metabolic and immunoregulatory programs in RORγt⁺ regulatory T cells during intestinal inflammation
- biorxiv2026-08-13score 80cardiologytherapeuticsOXPHOS
Pan-KDM inhibitor JIB-04 reverses MYH7-like HCM and restores mitochondrial respiration in iPSC-CMs
The pan-histone-lysine-demethylase inhibitor JIB-04 prevents and reverses hypertrophic cardiomyopathy in Myh6 R403Q/+ mice (the murine stand-in for human MYH7 R403Q). It cuts hypertrophy and fibrosis, preserves function, and fully prevents sudden death in cyclosporin A–accelerated disease; it also works after disease is established, after drug withdrawal, and in aged spontaneous HCM. In MYH7 R403Q iPSC-cardiomyocytes it normalizes disease genes, restores connexin-43 membrane localization, and improves mitochondrial respiration. PHF2 (KDM7C) is a candidate target in mouse and human HCM hearts.
Source preprint: Histone lysine demethylase inhibition is a disease-modifying therapy for hypertrophic cardiomyopathy
- biorxiv2026-08-11score 80protein importphospholipidsmetabolism
Djp1 delivers Psd1 and separately keeps mitochondrial phospholipid metabolism alive
The Hsp40 cochaperone Djp1, already known for ER-SURF handover of mitochondrial precursors, is a specific biogenesis factor for phosphatidylserine decarboxylase 1 (Psd1), the inner-membrane enzyme that makes mitochondrial phosphatidylethanolamine. That job depends on Psd1’s targeting signal and is not copied by other Hsp40s or ER-targeting factors. Losing Djp1 and Psd1 together is synthetically sick in a way that reveals extra, Psd1-independent roles for Djp1 in mitochondrial phospholipid metabolism.
Source preprint: Djp1 is a multifunctional Hsp40 cochaperone for mitochondrial phospholipid metabolism
- biorxiv2026-08-11score 80mtDNAtranslationreproduction
Sperm finish maturation by translating first in a leftover droplet, then on midpiece mitochondria
Transcriptionally silent, cytoplasm-stripped mammalian sperm still need about ten days of epididymal protein synthesis to become motile and fertile. Testicular sperm keep a cytoplasmic droplet with ribosomes and intact tRNAs and make protein there. In the epididymis that droplet fragments and synthesis moves to the midpiece, where mitochondrial translation turns on. Blocking cytosolic translation in testicular sperm or mitochondrial translation in epididymal sperm abolishes motility. Both apparatuses are required for maturation.
Source preprint: Life without cytoplasm: sperm sustain protein production utilizing cytoplasmic droplets and mitochondria as translational apparatuses
- biorxiv2026-09-10score 79mitophagyautophagymetabolism
ULK1 and ULK2 hold muscle size down by restraining mTORC1 and protecting mitochondrial protein turnover
The autophagy-initiating kinases ULK1 and ULK2 are a dual brake on skeletal-muscle growth: they keep autophagy running, hold mTORC1 in check, and help degrade mitochondrial and sarcoplasmic proteins. Lifelong loss makes fibers bigger and weaker; a few weeks of loss makes them bigger while force still holds.
Source preprint: ULK1 and ULK2 Restrain Skeletal Myofiber Growth by Balancing Protein Synthesis and Degradation
- biorxiv2026-09-04score 79neurobiologydevelopmentautonomic
Early-life adversity ages female vagal neurons along a mitochondrial-dysfunction path
Unpredictable maternal care permanently bends mouse vagal development. Heart-rate-variability trajectories split by sex: females mature too early then decline; males start blunt and recover. Female vagal neurons look mitochondrially broken, male neurons look mitochondrially adaptive, in different stretches of nucleus ambiguus.
Source preprint: Early Life Adversity Produces Enduring Molecular and Functional Disruption of Developing Vagal Circuits
- biorxiv2026-09-01score 79evolutionimportyeast
Forty percent of yeast de novo proteins are predicted to go to mitochondria
Across 332 Saccharomycotina yeasts, more than 5,000 robust de novo genes sit beside more than 10,000 extremely divergent novels. About 40% of de novo proteins are predicted mitochondrial versus 15% of divergent ones. Divergent proteins are longer and more disordered. New folds happen both ways, more often de novo, and some old folds are reinvented from noncoding DNA.
Source preprint: Evolutionary origins of protein novelty across an entire yeast subphylum
- biorxiv2026-08-26score 79OXPHOSmetabolismimmunology
After stem-cell transplant, jSSc monocytes quiet NF-κB and turn mitochondrial genes back on
In three children with juvenile systemic sclerosis, longitudinal CITE-seq of blood monocytes before autologous stem cell transplantation and at 6, 12, and 24 months after shows systemic-sclerosis-linked genes (including SERPINE1) falling, NF-κB inflammatory signaling decaying from a high baseline, and mitochondrial-function plus oxidative phosphorylation genes rising. An immune reset in this fibrotic disease is also a bioenergetic reset.
Source preprint: Longitudinal single-cell modeling reveals monocyte reprogramming in juvenile systemic sclerosis following autologous stem cell transplantation
- biorxiv2026-08-19score 79mito-nuclear communicationstress signalingchromatin
Mitochondrial stress signaling, not just chromatin logic, detaches heterochromatin after MRG-1 loss
In C. elegans, losing the euchromatic reader MRG-1 was thought to detach heterochromatin from the nuclear periphery by an unknown indirect route. That route is in part a mitochondrial stress response. The PMK-3/MAPK mitochondrial-stress regulator CBP-3 accounts for reporter detachment and about one-third of the transcriptional changes after mrg-1 depletion. Removing CBP-3 in MRG-1-deficient animals worsens mitochondrial dysfunction, fertility, and embryonic lethality, which means part of the “nuclear architecture defect” is an adaptive response to organelle stress.
Source preprint: Mitochondrial stress signaling shapes the nuclear response to loss of the chromatin reader MRG-1
- biorxiv2026-08-14score 79immunologyOXPHOSmetabolism
Mycoplasma gallisepticum raises itaconate in finch PBMCs and blocks the SDH-linked immune burst
In house finches, live Mycoplasma gallisepticum (MG) suppresses the early circulating immune-metabolic burst that heat-killed MG elicits. Heat-killed bacteria raise succinate dehydrogenase (SDH)-dependent respiration in peripheral blood mononuclear cells and cytokine genes in erythrocytes; live MG instead accumulates itaconate in PBMCs and skips those increases. Dimethyl itaconate copies the suppressed blood-cell phenotype. At the conjunctiva, live MG still raises mitochondrial respiration and cytokines. The pathogen looks like it commandeers an itaconate–SDH brake in circulating cells while allowing local inflammation at the infection site.
Source preprint: Mycoplasma gallisepticum uses itaconate-associated mitochondrial inhibition to suppress host immunometabolism
- biorxiv2026-08-14score 79islet biologydiabetesOXPHOS
MAFB knockdown in adult human α-cells collapses glucagon, identity, and respiration
In primary human pseudoislets, short hairpin RNA knockdown of the large MAF transcription factor MAFB impairs glucagon synthesis and secretion while barely touching insulin. Restricting the knockdown to CD26-positive α-cells shows a cell-autonomous failure of stimulus-secretion coupling, loss of canonical α-cell and neuroendocrine genes, ectopic mesenchymal and extracellular-matrix programs, and downregulation of electron-transport-chain genes in the largest α-cell subcluster that registers as weaker islet-wide mitochondrial respiration.
Source preprint: MAFB is essential for the maintenance of adult human α-cell identity and glucagon secretion
- biorxiv2026-08-10score 79OXPHOSredox biologysignaling
ADP keeps cytochrome oxidase’s nitrite-to-NO activity alive even in high oxygen, in an isoform-specific way
Detergent-solubilized yeast and mouse-brain cytochrome c oxidase (Cco) can reduce 1 mM nitrite to nitric oxide when driven by ascorbate/TMPD/cytochrome c. ADP and ATP gate that Cco/NO activity differently. ADP extends measurable NO formation across the whole oxygen range tested, up to 175 µM O2. ATP slightly inhibits Va-containing Cco and strongly stimulates Vb-containing Cco under anoxia. Cellular ADP/ATP and subsequently assayed Cco/NO both rise transiently after a hypoxic shift. The paper claims metabolic and isoform gating of catalytic capacity, not the enzyme’s share of cellular NO at physiological nitrite in coupled mitochondria.
Source preprint: Mitochondrial Signaling: Nitric Oxide Synthesis by Cytochrome c Oxidase and Its Oxygen Sensitivity Are Modulated by Adenine Nucleotides
- medrxiv2026-09-09score 78cell deathcancerimmunology
A mitochondria-dependent lytic death zone at the oral-cancer margin predicts immune exclusion and survival
In oral squamous cell carcinoma, a mitochondria-dependent lytic death program (mitoxyperilysis) organizes interferon-stimulated granulocytic suppressor cells and granzyme-B plasmacytoid dendritic cells into a barrier at the invasive edge. A five-gene signature taken from that network marks immune-desert tumors and splits survival on top of clinical stage.
Source preprint: A mitoxyperilysis-derived spatial signature predicts immune exclusion and survival in oral squamous cell carcinoma
- biorxiv2026-09-05score 78neurobiologybioenergeticsALS
Endogenous TDP-43 A315T in human cortical neurons wrecks respiration before it loses nuclear splicing
A human cortical-neuron line with endogenous ALS-linked TDP-43 A315T and a Dendra2 tag shows neurite loss, bad firing, and impaired mitochondrial respiration while nuclear cryptic-exon control still holds. Cytoplasmic aggregates need autophagy, stress granules rise, and the RNA chaperone Clip34 shrinks both aggregation and granule entry. Early toxic gain-of-function, not basal nuclear loss, is the first act.
Source preprint: A Human Neuronal Cell Model of Endogenous TDP-43 A315T Reveals Altered Protein Dynamics and Disease-Relevant Cellular Dysfunction
- biorxiv2026-09-03score 78immunologymitochondrial dynamicsgenetics
Plant ADF proteins keep PEN2-linked mitochondria off fungal entry sites and help Colletotrichum in
Subclass I actin depolymerizing factors (ADF1 through ADF4) in Arabidopsis thaliana act as susceptibility factors for the hemibiotrophic fungus Colletotrichum higginsianum. Losing ADF4, or silencing the whole subclass, blocks the actin-filament fragmentation that normally accompanies infection, lets PENETRATION 2 (PEN2)-associated mitochondria accumulate at attempted entry sites, and suppresses both penetration and secondary hyphae.
Source preprint: Arabidopsis thaliana ACTIN DEPOLYMERIZING FACTORs are novel susceptibility factors for Colletotrichum higginsianum
- biorxiv2026-09-03score 78metabolismhepatologyredox biology
Losing ER NADPH enzyme H6PD fills the liver with triglycerides and slows mitochondrial beta-oxidation
Hexose-6-phosphate dehydrogenase makes NADPH inside the ER. Knock it out in mice and the liver piles unsaturated long-chain triglycerides; Nile red agrees; proteomics turn fatty-acid pathways up. An AML12 CRISPR knockout accumulates lipid, cuts mitochondrial beta-oxidation, and the abstract cuts off mid-assay.
Source preprint: Hexose-6-phosphate dehydrogenase deficiency disrupts hepatic fatty acid homeostasis and induces triglyceride accumulation
- biorxiv2026-08-19score 78therapeuticscardiologyOXPHOS
Liver-approved PPAR-α/δ agonist elafibranor eases TGF-β1 fibrosis and restores respiration in human cardiac models
Elafibranor, a dual peroxisome proliferator-activated receptor alpha/delta (PPAR-α/δ) agonist already approved for liver disease, blunts transforming growth factor beta 1 (TGF-β1) fibrosis programs in human cardiac fibroblasts, spheroids, and contracting microtissues while partially restoring mitochondrial respiratory capacity, remodeling NAD and adenine-nucleotide pools, and recovering some calcium-handling and contraction parameters. That is a bioenergetic anti-fibrotic signal in human in-vitro systems, not a clinical cardiomyopathy trial.
Source preprint: The dual PPAR-α/δ agonist elafibranor attenuates TGF-β 1 -induced cardiac fibrosis through redox-metabolic and bioenergetic reprogramming in human cardiac models
- biorxiv2026-08-15score 78metabolismcancerNAD
Oncogenic tyrosine kinases phosphorylate NAMPT at Y188 and turn on NAD+ salvage, including at mitochondria
Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting NAD+ salvage enzyme, is a direct substrate of proto-oncogenic tyrosine kinases (ALK, insulin receptor, IGF1R, PDGFRA). Phosphoproteomics name Y188 as the major site, including on the fusion kinase NPM1::ALK. NAMPT meets NPM1::ALK in cytoplasm, nucleus, and mitochondria. Y188 phosphorylation raises catalytic activity, nicotinamide mononucleotide (NMN)/NAD+ biosynthesis, and downstream metabolism. A Y188F mutant or a dimerization break weakens enzyme, proliferation, and clonogenicity. NAMPT inhibition hits ALK-inhibitor-sensitive and -resistant lymphoma and pairs with ALK blockade.
Source preprint: Tyrosine phosphorylation and dimerization cooperatively activate NAMPT to enable NAD+ synthesis in cancer
- medrxiv2026-08-14score 78neurobiologymetabolismepigenetics
Early KAT6A truncations empty the gene; late ones invert neuronal metabolism and mitochondria
Arboleda-Tham syndrome is not one molecular disease. In patient iPSCs, early-truncating KAT6A variants (exons 1–15) are loss-of-function via nonsense-mediated decay; late-truncating variants (exons 16–17) escape NMD and act as gain-of-function. Those opposite mechanisms invert the direction of change in neuronal gene regulation, metabolism, and mitochondrial physiology, and they split facial gestalt and DNA-methylation episignatures. Therapy splits with them: inhibit KAT6A for late truncations; rescue dosage for early ones.
Source preprint: Dominant truncating variants in KAT6A cause two neurodevelopmental disorders with opposite gene regulatory and metabolic changes.
- biorxiv2026-08-08score 78neurobiologyOXPHOSmetabolism
Visual cortex sits on mitochondria-poor tissue; semantic cortex sits on mitochondria-rich tissue
7T fMRI during natural-scene viewing, split by image-to-brain encoding into variance unique to visual versus semantic features, was compared with postmortem mitochondrial atlases under spatial-autocorrelation-preserving inference. Visual-specific cortical variance aligns negatively with mitochondrial density and respiratory capacity. Semantic-specific variance aligns positively with mitochondrial density. Transcriptomic enrichments run in opposite mitochondrial and cellular programs along those two representational axes. How cortex represents the world tracks how the tissue is provisioned with mitochondria.
Source preprint: Distinct mitochondrial phenotypes align with visual and semantic representations across human cortex
- biorxiv2026-09-16score 77immunometabolismOXPHOStherapeutics
AS-3 turns RAPTOR-mTORC1 on in CD8 T cells, lifting mitochondrial metabolism and adoptive therapy
Adoptive cell therapy fails when expanded CD8 T cells lose metabolic fitness. AS-3, found by phenotypic screening and medicinal chemistry, is a small-molecule RAPTOR-dependent activator of mechanistic target of rapamycin complex 1 (mTORC1). It raises effector cytokines without killing the cells, pushes glycolysis and mitochondrial oxidative phosphorylation, keeps signaling alive under rapamycin, and improves two independent adoptive-therapy models with more persistence and less exhaustion.
Source preprint: Discovery of a Small-Molecule mTORC1 Pathway Activator that Enhances Adoptive T-Cell Therapy via Immuno-metabolic Reprogramming of CD8+ T Cells
- biorxiv2026-09-10score 77cell deathcancerredox biology
Melittin kills liver-cancer cells through mitochondrial ROS and gasdermin E, not only by ripping the plasma membrane
The bee-venom peptide melittin, textbook membrane detergent, drives pyroptosis in hepatocellular carcinoma cells via mitochondrial oxidative stress and gasdermin E (GSDME) cleavage. Scavenge mitochondrial reactive oxygen species (mtROS) with Mito-TEMPO and the lytic death retreats. The peptide still punches membranes. It also turns the mitochondrion into the match.
Source preprint: Melittin-induced membrane disruption in hepatocellular carcinoma involves mtROS/GSDME-mediated pyroptosis
- biorxiv2026-09-04score 77metabolismimmunologyOXPHOS
Tirzepatide keeps hematopoietic progenitors cycling and OXPHOS-competent while cutting inflammatory monocytes
Matched weight loss in obese mice splits by method. Caloric restriction empties blood lineages and shuts HSPC nutrient-sensing, proliferation, and oxidative phosphorylation. Tirzepatide keeps blood counts, preserves more progenitor cycling and OXPHOS, and specifically cuts Ly6C-high CCR2-positive monocytes. Those monocytes bounce back when the drug stops.
Source preprint: Tirzepatide preserves hematopoietic stem and progenitor cycling while remodeling inflammatory monocytes in obese mice
- biorxiv2026-08-21score 77agingtherapeuticsredox biology
TLR2 plus peroxide senescence in human disc cells opens a metabolic-activity window for senolytic screens
Cherif and colleagues build a standardized senescence recipe for primary human intervertebral disc cells — TLR2 ligand plus tert-butyl hydroperoxide — and show that Alamar Blue can find a senolytic therapeutic window. Outer annulus fibrosus cells senesce hardest. o-Vanillin, RG-7112, and ABT-199 drop metabolic activity in mixed senescent cultures without killing non-senescent cells, and those drops track β-galactosidase and p16.
Source preprint: A Standardized In Vitro Platform for Senolytic Drug Discovery in Human Musculoskeletal Cells
- biorxiv2026-08-21score 77mitochondrial transferlaborimmunology
M1 macrophages tunnel mitochondria into uterine myocytes and trigger progesterone withdrawal
Pro-inflammatory M1 macrophages, but not M2 macrophages, form tunneling nanotubes with uterine myocytes and transfer mitochondria in one direction. That transfer raises myocyte ATP and 20α-hydroxysteroid dehydrogenase, metabolizes progesterone, and increases progesterone-receptor A phosphorylation, producing intracellular and functional progesterone withdrawal. In pregnant mice, monocytes that carry Dendra-labelled mitochondria are recruited to the myometrium, become M1 macrophages, and hand mitochondria to myocytes before labor starts.
Source preprint: Macrophage to Myocyte Mitochondrial Transfer in the Myometrium: A Novel Mechanism for the Initiation of Labor
- biorxiv2026-08-15score 77metabolismOXPHOSproteostasis
Z-AAT polymers clog hepatic lipid handling and leave mitochondria numerous but respiratory-poor
Z-variant alpha-1 antitrypsin (Z-AAT) polymers accumulate in Z-HepG2 cells and patient-derived ZZ hepatic organoids, cut secretion, and bring lipid storage, mitochondrial structural abnormalities, more mitochondria with less respiratory capacity, reduced oxidative phosphorylation, a partial glucose lean, and increased peroxisomal mass. Controls mount an adaptive mitochondrial transcriptional response to lipid supplementation; Z-HepG2 cells barely do. Proteotoxic AATD liver disease is also a failure of organelle metabolic flexibility.
Source preprint: Z-AAT impairs organelle homeostasis and reduces adaptive response to lipids in alpha-1 antitrypsin deficiency models
- biorxiv2026-09-08score 76translationcancermetabolism
eIF4A inhibitors starve BRAF-resistant melanoma of translation and of mitochondrial metabolic output
Kinase-inhibitor-resistant BRAF-mutant melanoma still depends on eIF4A-driven mRNA translation. Blocking that helicase (CR-1-31-B) cuts survival proteins, flattens a high-output mitochondrial/metabolic state, restricts glutamine carbon past uptake, and deepens BRAF-inhibitor control in xenografts.
Source preprint: eIF4A inhibition disrupts resistance-associated translational and metabolic programs in BRAF-mutant melanoma
- biorxiv2026-09-03score 76bioenergeticsinfectionfungi
Cryptococcal Yck2 sits on mitochondria and the proton pump, and losing it raises mitochondrial ROS
The casein kinase Yck2 in Cryptococcus neoformans, already a druggable virulence node, proximity-labels mitochondrial proteins and the plasma-membrane H+ ATPase Pma1. Without Yck2, cells are sensitive to mitochondrial inhibitors, make more mitochondrial ROS, and run a higher intracellular pH. Cell wall, drugs, and temperature phenotypes now have an organelle-and-pH fuse.
Source preprint: Yck2 links mitochondrial function and pH homeostasis to cell wall remodeling and antifungal susceptibility in Cryptococcus neoformans
- biorxiv2026-08-20score 76proteostasisredox biologymetabolism
Peroxide cataracts in zebrafish switch on the unfolded and mitochondrial unfolded protein responses
Hydrogen peroxide injected into the aqueous humor of adult zebrafish produces cortical cataracts and a cortex proteome that activates the unfolded and mitochondrial unfolded protein responses, alongside energy-metabolism, calcium, degradation, and remodeling shifts. Crossing reduced NRF2 defense with a crystallin/proteostasis mutant (cryaba) is meant to mimic aged human lenses. The mitochondrial claim is not that the lens is a new OXPHOS organ, but that mitoUPR joins UPR as a candidate therapeutic axis in oxidative cataract.
Source preprint: Upregulation of the Unfolded and Mitochondrial Unfolded Protein Responses in Oxidative Stress-Induced Cataract
- biorxiv2026-08-13score 76mitochondrial dynamicssignalingneurobiology
PKA anchored at AKAP1 remakes mitochondrial shape; the same kinase on MAP2 is a structural microtubule brace
A SpyCatcher-SpyTag replacement lets researchers keep an AKAP’s environment and toggle type-II PKA RII anchoring. RII on AKAP79 or AKAP1 gives phosphorylation-dependent outcomes, including catalytic-subunit membrane recruitment and mitochondrial morphology regulation (AKAP1). RII on MAP2 straightens microtubules, widens bundles, and supports dendritic arborization without needing phosphorylation; the structural job wants an intact second cAMP-binding pocket and is recapitulated by native MAP2–RII. Anchored PKA is sometimes an enzyme and sometimes a cAMP-gated structural protein. Mitochondria are one of the enzymatic addresses.
Source preprint: PKA can adopt structural or enzymatic roles depending on its anchoring site
- biorxiv2026-09-01score 75methodsnephrologytoxicology
Proxiloid kidney tubules catch adefovir mitochondrial toxicity that rodent tests missed
Human iPSC proxiloids become lumenized, polarized proximal-tubule organoids in 14 days with transport and oxidative metabolic competence. They see aminoglycoside injury better than matched 2D cultures and flag adefovir mitochondrial toxicity that rodents missed. A scalable NAM for PT drugs that hit mitochondria.
Source preprint: Scalable proxiloids enable human-relevant assessment of kidney proximal tubule toxicity
- biorxiv2026-08-17score 75neurobiologymtDNAmetabolism
Fractionated 20 Gy X-rays senesce F11 sensory neurons and raise mtDNA copy number without a ROS or OCR hit
Four daily 5 Gy X-ray fractions (20 Gy total) leave F11 dorsal-root-ganglion neuron-like cells senescent, with higher mitochondrial DNA copy number and a shifted NAD+/NADH pathway, but without a change in oxygen consumption rate or an oxidative-stress signal 24 hours after the last dose. Gene-expression changes land on mechanoreceptor-fiber programs that can be pro-nociceptive. Radiotherapy-linked chronic pain, in this cell line, is not a simple mitochondrial ROS story.
Source preprint: Fractionated ionising radiation affects cellular functions, and gene expression associated to subpopulation of F11 dorsal root ganglia neurons without inducing oxidative stress
- biorxiv2026-09-09score 74metabolismcancermtDNA
IDH1-mutant gliomas split into quiet mitochondrial one-carbon states and a high-OCM subset that dies sooner
IDH1-mutant gliomas are not one metabolically meek tumor. A 64-gene one-carbon-metabolism score on 709 TCGA/CGGA cases, plus U87 R132H cells, splits a suppressed, mitochondrially compensated state from an aggressive subset that hyperactivates proliferative one-carbon genes and has worse survival (CGGA hazard ratio 1.61).
Source preprint: One-Carbon Metabolic Reprogramming Stratifies Prognosis and Defines Distinct Biological States in IDH1-Mutant Gliomas
- biorxiv2026-09-04score 74aginggliaredox biology
Doxorubicin and high glucose both senesce human microglia, but only high glucose turns NRF2-TFAM on
HMC3 microglia senesce under chronic doxorubicin or high glucose: hypertrophy, SA-beta-gal, less viability, p53-p21, lingering DNA-damage signaling. Metabolic stress also induces p16 and parks p21 at the nuclear rim. Mitochondria move in both cases: doxorubicin turns NRF2-TFAM down; high glucose turns that axis on and raises KEAP1, an antioxidant reply that still fails to restore mitochondrial content.
Source preprint: Genotoxic and metabolic stress drive divergent senescence programs in human microglia
- biorxiv2026-09-02score 74mitochondrial dynamicscomputationalstructural biology
PRISM stably paints mitochondria with four other organelles and returns 500-plus contact metrics per cell
A single PiggyBac-integrable cassette (PRISM: Plasmid-based Reporter for Intracellular Spectral Microscopy) stably labels mitochondria, Golgi, peroxisomes, endoplasmic reticulum, and lysosomes for spectral microscopy, then a modular pipeline extracts more than 500 morphology, distribution, pairwise, and higher-order contact metrics per cell. The authors use it to score cytoskeletal perturbation, phosphatidylinositol 4-phosphate redistribution after lysosomal damage, and organelle-network remodeling during Zika virus infection.
Source preprint: PRISM: A Plasmid-based Reporter for Intracellular Spectral Microscopy
- biorxiv2026-08-19score 74mitophagyautophagystructural biology
Atg11’s Z-shaped N-terminus holds a basic pocket that grabs Atg9 and licenses mitophagy
In yeast selective autophagy, Atg11’s N-terminal domain is the primary Atg9-binding site, but it needs C-terminal clustering to bind completely. Cryo-EM plus AlphaFold reveal a conserved, positively charged pocket on the Z-shaped NTD that is essential for Atg9. Mutating that pocket loses Atg9 binding and reduces selective autophagy of mitochondria. Atg9 vesicles are the first membrane of the autophagosome; this is how the scaffold recruits them.
Source preprint: The Z-shaped N-terminal Domain of Atg11 Coordinates Atg9 Recruitment in Selective Autophagy
- biorxiv2026-08-13score 74cancerredox biologyhypoxia
Baicalein plus thermal cycling kills hypoxic A549 cells by dropping HIF-1α/SOD2 and collapsing mitochondrial potential
Under cobalt chloride hypoxia, the flavonoid baicalein plus thermal-cycling stimulation (TCS) cuts A549 non-small-cell lung-cancer viability and drives apoptosis while largely sparing IMR-90 lung fibroblasts. The pair suppresses hypoxia-inducible factor 1-alpha (HIF-1α) and mitochondrial superoxide dismutase 2 (SOD2), raises reactive oxygen species, downregulates the sanitizing enzyme MutT homolog 1 (MTH1), drops mitochondrial membrane potential, and increases poly(ADP-ribose) polymerase (PARP) cleavage.
Source preprint: Combined effect of baicalein and thermal-cycling stimulation on suppressing non-small cell lung cancer A549 cells under CoCl 2 -induced hypoxia
- biorxiv2026-09-17score 73mtDNAevolutionmito-nuclear
Broom and Italian hares captured a mountain-hare mitogenome with a matching nuclear payload
Two sister hares, Lepus castroviejoi in Iberia and Lepus corsicanus in Italy, carry fixed mitochondrial genomes from the mountain hare Lepus timidus. Whole mitogenomes, including Iron Age samples, date that capture in their common ancestor. Coalescent modeling of complete genomes puts a roughly 24 percent mountain-hare nuclear contribution near 900 thousand years ago, and about 17.8 percent of autosomes still look introgressed, close to the 18 percent expected under drift. Highly introgressed, gene-dense segments include mitochondrial-function genes that echo mito-nuclear candidates in the Iberian hare.
Source preprint: Extensive nuclear introgression accompanied ancient mitochondrial capture in the common ancestor of two sister hare species
- biorxiv2026-09-08score 73neurobiologygliaaging
Old male brains, stripped of microglia, downregulate mitochondrial ATP-synthesis proteins
When 21-month-old mice lose microglia to CSF1R blockade, both sexes drop microglia-enriched microRNAs, but the proteome diverges hard: 295 changing proteins in males versus 34 in females. Male synaptic-vesicle proteins go up; mitochondrial ATP-synthesis machinery goes down. Microglial absence in the aged brain is a sex-specific bioenergetic event.
Source preprint: Sex-divergent responses to microglial depletion suggest distinct regulatory dependencies in the aged brain
- biorxiv2026-09-02score 73lipidgliacontact sites
Linoleic acid and LPG 16:0 tether microglial lipid droplets to mitochondria after subarachnoid bleed
CSF linoleic acid is high after aneurysmal SAH. In mice and hemoglobin-hit microglia, an LA to lysophosphatidylglycerol 16:0 to PPAR-delta path is proposed to stabilize a noncanonical mitochondrial PPAR-beta/delta, tether lipid droplets to mitochondria, and ease microglial failure. The posted abstract is truncated before the full mechanistic numbers.
Source preprint: Linoleic Acid-Lyso PG Axis promoting lipid droplet–mitochondria tethering by stabilizing Noncanonically Mitochondrial PPAR β/δ to Ameliorate Microglial Dysfunction in subarachnoid hemorrhage
- biorxiv2026-08-17score 73neurobiologyredox biologypain
Schwann-cell p75NTR turns NGF into mitochondrial ROS and TRPA1-dependent persistent pain
Nerve growth factor (NGF) pain splits by receptor and cell. Neuronal TrkA carries acute nociception and heat hyperalgesia. Mechanical allodynia and cold hypersensitivity require p75NTR on Schwann cells. There, NGF and proNGF trigger p75NTR-dependent calcium release, TRPA1 activation, mitochondrial reactive oxygen species, and NOX1-dependent oxidative amplification. Blocking ROS or TRPA1, or deleting Trpa1 in Schwann cells, cuts mechanical and cold pain without touching the acute/heat TrkA program. Cleavage-resistant proNGF only evokes the p75NTR half.
Source preprint: Schwann cell p75NTR sustains persistent pain downstream to NGF through ROS-dependent TRPA1 signaling
- medrxiv2026-08-17score 73cardiologymetabolismcomputational
A 4.5-million-person HF GWAS puts myocardial energy, the mitochondrial proteome, and adipokines on the target list
Multi-ancestry GWAS of 345,687 heart-failure cases among 4,468,166 people, plus HFpEF and HFrEF splits, with plasma proteomics and multi-tissue transcriptomics, yields 383 loci (166 new) and 568 genes (375 new). Eleven new genes are already drug targets, including a case for expanding aldosterone-synthase inhibitors (CYP11B2) and type-II activin-receptor antagonists (ACVR2A) into HF. Nearly 100 genes sit in food intake, energy expenditure, fatty-acid/glucose/BCAA metabolism, and the mitochondrial proteome that sustains myocardial ATP. Metabolism and adipokines are framed as primordial HF targets.
Source preprint: Global genomics in over 4 million individuals prioritizes therapeutic targets for heart failure and its subtypes
- biorxiv2026-08-16score 73cancermetabolismhypoxia
IL-1β drives colorectal glycolysis and suppresses mitochondrial respiration through AKT then HIF-1α
Interleukin-1 beta (IL-1β), a cytokine elevated in colorectal cancer, stimulates glycolysis, inhibits maximal mitochondrial respiration, and raises AKT phosphorylation and hypoxia-inducible factor 1-alpha (HIF1α). Knockouts split the pathway: AKT1/2 sit upstream of HIF1α. IL-1β still phosphorylates AKT without HIF1α, but cannot raise HIF1α protein without AKT1/2. Tumor necrosis factor alpha (TNFα) uses the same AKT–HIF1α route to increase glycolysis. The paper also says IL-1β suppresses oxidation of the fiber-derived nutrient butyrate.
Source preprint: Requirement of hypoxia-inducible factor 1 alpha for interleukin 1 beta induced glycolysis in colorectal cancer cells
- biorxiv2026-08-13score 73infectionquality controlapoptosis
KSHV vBcl-2 pulls KLHL9 to mitochondria and needs that host adaptor for lytic yield
Kaposi’s sarcoma-associated herpesvirus (KSHV) viral Bcl-2 (vBcl-2) is required for infectious-particle production by a function that is independent of its apoptosis/autophagy roles. Proteomics of HA-vBcl-2 pulldowns identify the Cullin 3-RING ligase adaptor KLHL9. The two proteins co-immunoprecipitate, and during lytic reactivation KLHL9 moves from a cytoplasmic/perinuclear pattern onto mitochondria that overlap HA-vBcl-2. CRISPR loss of KLHL9 cuts lytic proteins and progeny; sgRNA-resistant KLHL9 partially restores both. vBcl-2 is not a detectable KLHL9 ubiquitin substrate.
Source preprint: KLHL9 acts as a KSHV vBcl-2-interacting host factor that supports lytic replication
- biorxiv2026-09-08score 72methodsneurobiologyOXPHOS
A widely used TBI atlas called microglia neurons, then invented a KCNC3 OXPHOS signature
Most cells labeled “glutamatergic neuron” in CEREBRI, the dominant single-cell traumatic-brain-injury atlas, are glia. That contamination manufactured a biphasic ion-channel trajectory and a KCNC3-specific oxidative-phosphorylation signature that vanish when the labels are audited. Mitochondrial stories in public atlases are only as good as the cell-type names.
Source preprint: AnnoAudit: a marker-based protocol for auditing single-cell atlas annotations reveals annotation-driven artifacts in a widely used traumatic brain injury resource
- biorxiv2026-09-03score 72nephrologyOXPHOStherapeutics
DVA proteomics in CKD restores OXPHOS proteins and turns down Rho-GTPase inflammatory cytoskeleton programs
DIA proteomics of a CKD model with DVA, KY, and combo arms finds a cluster of mitochondrial/OXPHOS/metabolic proteins that CKD turns down and DVA turns back up, and a second cluster of immune, oxidative-stress, and cytoskeletal proteins that CKD turns up and DVA turns down. The title's mitochondrial restoration is that first cluster.
Source preprint: Systems-level proteomic reprogramming reveals mitochondrial restoration and inhibition of Rho GTPase-mediated cytoskeletal and inflammatory signaling in CKD
- biorxiv2026-09-02score 72metabolismOXPHOSgenetics
The rat jaw opener transcribes mitochondrial energy and fatty-acid modules the closer does not
All three rat feeding muscles (anterior digastric, superficial masseter, sternohyoid) express mostly fast-twitch contractile isoforms, but the jaw-opening anterior digastric downshifts several myosin and tropomyosin families, upshifts slower or oxidative myosins (Myh7, Myh2), and is the muscle whose co-expression modules are enriched for fatty-acid catabolism, mitochondrial energy production, and vascular or extracellular-matrix remodeling.
Source preprint: Transcriptomic profile of a rat jaw opener (anterior digastric) and a jaw closer (superficial masseter).
- biorxiv2026-08-25score 72redox biologymetabolismtherapeutics
Thiol-coated iron oxide nanoparticles chelate copper and put tomato mitochondria back to work
MPA-iron oxide nanoparticles sequentially coated with chitosan, glutathione, and 3-mercaptopropionic acid bind more copper than bare iron oxide, lower intracellular reactive oxygen species, restore mitochondrial membrane potential, and rescue germination plus root and shoot growth in copper-stressed tomato (Solanum lycopersicum) seedlings. The plant mitochondrion is treated as the first organelle copper wrecks, and as a readable endpoint for a dual chelator-antioxidant particle.
Source preprint: Efficient Mitigation of Copper Induced Cellular Dysfunction Using Chitosan Based Iron Oxide Nanoparticles
- biorxiv2026-08-21score 72neurobiologymitoUPRquality control
Without ATFS-1, worm dopamine neurons need JMJD histone demethylases and TWK-14 to survive α-synuclein
α-Synuclein overexpression in C. elegans chronically turns on the mitochondrial unfolded-protein response and worsens dopaminergic neuron loss. A loss-of-function atfs-1 mutation, which disables that UPRmt transcription factor, is neuroprotective. An F3 screen in that protected background recovered nonsense alleles of the H3K27me3 demethylases jmjd-1.2 and jmjd-3.1 and of the K+ leak-channel gene twk-14. Depleting any of the three in dopamine neurons restores neurodegeneration in the α-syn + atfs-1(lf) background. Those gene products therefore confer protection from α-synuclein once UPRmt is off.
Source preprint: An atfs-1 loss-of-function screen identifies novel regulators of a-synuclein toxicity in C. elegans dopaminergic neurons
- biorxiv2026-08-19score 72neurobiologyredox biologyproteostasis
VCP inhibitor ML240 saves photoreceptors, not RPE, and keeps cytochrome c in inner segments
In a human iPSC-RPE plus porcine neuroretina co-culture, the cigarette-smoke oxidant hydroquinone (HQ) stresses both RPE and photoreceptors, drives caspase apoptosis, ER-associated degradation in photoreceptors, thinner outer nuclear layer, and shorter outer segments. The VCP inhibitor ML240 does not stop HQ apoptosis in iPSC-RPE, but it preserves photoreceptor outer-segment length and cone density. Proteomics show lower ERAD markers, higher antioxidant proteins, and preserved cytochrome c enrichment in inner segments, read as improved mitochondrial integrity.
Source preprint: VCP inhibition preserves photoreceptor integrity under hydroquinone-induced oxidative stress in a human iPSC-RPE/porcine neuroretina co-culture model
- biorxiv2026-08-14score 72neurobiologytherapeuticsophthalmology
Cumulative IOP above 19 mmHg times RGC death; a mitochondria-targeted peptide still cuts the hazard
In DBA/2J glaucoma mice, retinal ganglion cell (RGC) loss is modeled as a latent time-to-event process driven by monthly intraocular pressure (IOP). Across Cox and Andersen–Gill models, cumulative IOP burden above 19 mmHg dominates the hazard. Peak and contemporaneous IOP add little once sustained exposure is in the model. HDAP2, a mitochondria-targeted neuroprotective peptide, significantly reduces progression hazard after adjustment for that longitudinal IOP exposure, which argues for a pressure-independent, organelle-directed effect.
Source preprint: Modeling Retinal Ganglion Cell Degeneration from Longitudinal Intraocular Pressure Trajectories
- biorxiv2026-08-13score 72neurobiologyagingmetabolism
CASIN restores aged α-synuclein brain networks along EGFR–PI3K–MAPK routes that feed mitochondria
In an inducible alpha-synuclein oligomer mouse, motor rescue by the CDC42 inhibitor CASIN is age-dependent, and single-nucleus RNA-seq now maps the transcriptional undo. CASIN robustly reverts Parkinson-related programs at 24 months; aging programs are loudest at 16 months. Networks converge on MAPK and PI3K/AKT, and the authors nominate an EGFR–PI3K–MAPK axis as the route by which CDC42 blockade may restore mitochondrial and synaptic function in aging and Parkinson disease.
Source preprint: Targeting CDC42 with CASIN Reprograms Cell Type Specific Transcriptomes and MAPK Driven Transcription Factor Networks in the Aging Brain
- biorxiv2026-08-13score 72therapeuticscancerproteostasis
ClpP-activating imipridones ONC206/ONC212 plus lurbinectedin synergize on PDAC cells
Next-generation imipridones ONC206 and ONC212, which activate the mitochondrial ClpP protease and the integrated stress response, kill pancreatic ductal adenocarcinoma lines at sub-micromolar 72-hour IC50s (ONC212 stronger) and synergize with the RNA-polymerase-blocking drug lurbinectedin (HSA synergy up to 29.5). Apoptosis runs through ClpX depletion, ATF4 induction, and caspase PARP cleavage. The ONC212–lurbinectedin pair raises DR5 and lowers Bcl-2 and ClpX. Non-malignant CCD 841 CoN colon epithelial cells are largely spared.
Source preprint: Next-Generation Imipridones ONC206 and ONC212 Synergize with Lurbinectedin in Killing Pancreatic Ductal Adenocarcinoma Cells
- biorxiv2026-08-10score 72agingmitochondrial dynamicsneurobiology
Nuclear troponin I/UNC-27 turns on in adult muscle and its arrival fragments mitochondria
In C. elegans, sarcomeric transcripts start falling at the onset of adulthood. A visual screen for delayed muscle ageing maps to troponin I (unc-27), a contractile protein, at a single amino acid in a predicted nuclear localization signal. UNC-27 enters muscle nuclei from early adulthood via multiple NLS motifs. Blocking that nuclear entry preserves sarcomeric gene expression and delays proteostatic imbalance and mitochondrial fragmentation. Nuclear UNC-27 selectively regulates structural muscle-apparatus genes. Mammalian troponin I orthologues also carry NLS motifs.
Source preprint: A nuclear role for the contractile protein troponin I/UNC-27 in regulating muscle aging in C. elegans
- biorxiv2026-09-07score 71stem cellsmetabolismmethods
Culture-acquired BCOR truncations lock human iPS cells into a mitochondrial-metabolism-high adaptive state
The most recurrent culture mutations in human induced pluripotent stem cells are BCOR exon-7 truncating indels, a spectrum unlike BCOR in cancer. Losing BCOR rewires chromatin, RNA, and protein toward developmental, pluripotency, and mitochondrial-metabolism programs. CRISPR correction only partly walks it back, so the adaptive state persists after the allele is gone.
Source preprint: BCOR mutations establish a persistent culture-adaptive state in human induced pluripotent stem cells
- biorxiv2026-09-03score 71cardiologymetabolismlipid
Sex and NOS dose split older mice into HFpEF-like females and HFrEF-like males under fat plus L-NAME
Older mice on high-fat diet plus NOS inhibition do not make one heart-failure model. Low-dose L-NAME females get diastolic failure with preserved systole. High-dose males get hypertension and systolic failure. Lipidomes share sphingolipid and phospholipid remodels with sex-specific phosphatidylinositol and lysophosphatidylcholine species. Transcriptomes share matrix, calcium-handling, and metabolic paths.
Source preprint: Nitric oxide synthase inhibition and biological sex define different cardiac responses to cardiometabolic stress in older mice.
- biorxiv2026-08-17score 71metabolismredox biologysignaling
Alpha cells bank pentose-phosphate redox at higher glucose so glucagon still fires when sugar falls
Live-cell redox imaging in alpha cells inside intact islets shows that glucose flux through the pentose phosphate pathway raises cytosolic redox potential. That prior redox charge, not a simple low-glucose mitochondrial story, helps keep protein kinase A (PKA) on and glucagon available during hypoglycemia. Antioxidants and a 5 mM glucose pre-incubation manipulate the charge; whole-body redox state changes the mouse counterregulatory response. The authors explicitly ask whether non-mitochondrial glucose metabolism potentiates glucagon at low glucose.
Source preprint: Glucose derived redox equivalents preserve PKA activity and glucagon secretion during hypoglycaemia
- biorxiv2026-08-19score 70mtDNAevolutiontranslation
Anomiida bivalves rewrite the mitochondrial code: TAA as tyrosine, plus frameshifting
Phylogenomics elevate the APPD bivalve clade (Anomiidae, Placunidae, Plicatulidae, and inferred Dimyidae) to Anomiida ord. nov., sister to Limida and Pectinoidea at about 428 million years. Their mitochondrial genomes show extreme translational plasticity: Pododesmus uses the invertebrate mitochondrial code; Heteranomia uses +1 frameshifting to skip in-frame TAG; Anomia, Enigmonia, Placuna, and Plicatulidae reassign TAA to tyrosine, confirmed by proteomics. That is a new bivalve translation table, sitting next to massive chromosomal fusions (6–13 chromosomes versus 20 ancestral molluscan linkage groups).
Source preprint: Life finds a way: Integrative phylogenomics resolves an overlooked bivalve order with chromosome fusion and mitochondrial translational-code evolution
- biorxiv2026-08-14score 70immunologymetabolismredox biology
Severe endometriosis lesion vesicles enter endothelial mitochondria and push angiogenesis
Small extracellular vesicles from endometriosis patients change with stage and source. Lesion-derived vesicles lose epithelial surface markers, gain immune signatures, and, when they come from severe disease, show enhanced uptake and mitochondrial localization in human uterine microvascular endothelial cells and promote angiogenesis. Plasma vesicles shift adhesion- and platelet-associated profiles. Multi-omics add coordinated immune, matrix, epithelial, vascular, oxidative-stress, and metabolic programs. The mitochondrial claim is trafficking-plus-function in endothelial cells, not a respiratory-chain map of the lesion.
Source preprint: Endometriosis patient-derived small extracellular vesicles carry unique immune, proteomic and lipidomic signatures associated with mild and severe endometriosis
- biorxiv2026-08-13score 70endosymbiosismtDNAinfection
Australian tick metagenomes recover Midichloria that still look built for life inside mitochondria
Shotgun metagenomes from four Australian tick species yield six MAGs: Coxiella-like endosymbionts, a facultative Rickettsia, and two Midichloria mitochondrii strains (Ixholo1, Ixholo2). The symbionts lack obvious virulence factors and keep B-vitamin and/or heme genes, plus CLE shikimate genes tied to serotonin and blood feeding. Pangenomics suggest Midichloria may be more than one species, and Ixholo2 retains genes associated with an intramitochondrial lifestyle. Tick “microbiomes” here are nutritional, sometimes intra-organelle, partners.
Source preprint: Characterisation and genomic analysis of bacterial nutritional endosymbionts in Australian ticks from shotgun metagenomic sequencing
- biorxiv2026-08-11score 70mtDNAcomputationalpopulation genetics
Medieval Sigtuna ivory is half eastern Atlantic walrus; attached rostra were a western trade
Earlier ancient-DNA work made medieval European walrus look almost entirely Greenlandic because it sampled decorated rostra (skulls with paired tusks). Workshop offcuts from Sigtuna, plus a genome-wide split between western and eastern Atlantic walrus populations (144,986 diagnostic nuclear SNPs, usable on low-coverage data), change that. All medieval rostra still assign west. About half the Sigtuna ivory assigns east, including Iceland and the Barents Sea, and the eastern objects come earlier. Mitochondrial DNA alone could not resolve this. The ivory trade was sequential and broader than the rostrum trade.
Source preprint: Of bone and ivory: Eastern Atlantic sources of the medieval European walrus ivory trade discovered by ancient mitochondrial and nuclear DNA
- biorxiv2026-08-11score 70metabolismautophagylipid droplets
Vlf1, found because LD-less mitochondria look wrong, is a vacuolar brake on yeast lipophagy
Yeast that cannot make neutral lipids, and therefore lack lipid droplets, change many proteins in isolated mitochondrial fractions. Among downregulated proteins is Ylr001c, renamed Vlf1 (Vacuolar Lipophagy Factor 1). Vlf1 is glycosylated and vacuolar, not whatever earlier localizations said. It binds the autophagic lipase Atg15, tunes rapamycin sensitivity, and is the first named vacuolar lipophagy regulator in S. cerevisiae: no Vlf1, more autophagy/lipophagy; extra Vlf1, less. Mitochondria were the discovery compartment, not the home.
Source preprint: Characterization of Vlf1 as a regulator of lipophagy
- biorxiv2026-08-19score 69developmentmetabolismproteostasis
Oocyte DHX36 keeps mitochondria, membranes, and microvilli intact so follicle signals can be delivered
Oocyte-specific deletion of the G-quadruplex helicase DHX36 wrecks antral follicle development and hormone-induced ovulation. Granulosa cells fail to proliferate and cumulus fails to expand because SMAD2/3 and SMAD1/5/8 do not activate, even though major oocyte-secreted factors are still expressed. The delivery hardware is broken: microvilli and transzonal projections. Proteomics, lipidomics, and ultrastructure show disordered phospholipid metabolism, autophagy, and organelle homeostasis, including abnormal mitochondria, lysosomes, and ER. Promoters of the downregulated genes are G4-rich.
Source preprint: DHX36 regulates antral follicle development and ovulation as a non-OSF maternal factor by maintaining oocyte homeostasis and supporting OSF delivery
- biorxiv2026-08-21score 68metabolismredox biologybioprocess
Late CHO fed-batch cells burn fat in mitochondria and peroxisomes, then flirt with ferroptosis
Across ambr250 CHO fed-batch conditions, cultures follow a conserved path: proliferate, transition, then a high-stress end state of mitochondrial and peroxisomal fatty-acid β-oxidation, lipid remodeling, oxidative burden, and ferroptosis-associated pathways. Richer feeds delay that switch via redox/glutathione defense but do not raise antibody titre in proportion. Survival spends the resources that would have been titer. Fatty-acid oxidation and ferroptosis are the late-stage constraints to engineer against.
Source preprint: Fatty Acid β-oxidation and Ferroptosis Define a Survival-Productivity Trade Off in CHO fed-Batch Bioreactors
- biorxiv2026-08-21score 68diabetesskeletal muscleOXPHOS
In 301 muscle biopsies, type 2 diabetes dysregulates fiber mitochondria and splicing
Weighted gene co-expression analysis of 301 living-donor skeletal-muscle biopsies yields 56 modules that, mapped onto single-nucleus RNA-seq cell-type signatures, show type 2 diabetes associated with muscle-fiber mitochondrial function and messenger-RNA splicing, endothelial vascularization and phospholipase D signaling, and macrophage- and T-cell-associated inflammation. Candidate drivers include ATP5L, ATF2, SIRT1, and THRAP3 in fibers; JAM2 and CLEC14A in endothelium; and F13A1 and IRF8 in immune cells. Fiber and endothelial modules are enriched for type 2 diabetes and related-trait genome-wide association signals in a single-nucleus ATAC-seq overlay.
Source preprint: Integrated Analysis of Skeletal Muscle Transcriptional Networks Characterizes Dysregulation in Pathways and Trait-Associated Regulatory Regions in Type 2 Diabetes
- biorxiv2026-08-19score 68mtDNAagingevolution
Long-lived termites write a stronger mitochondrial A>G signature all the way into the proteome
An age-associated mitochondrial A>G mutational signature, first described in mammals, is stronger in long-lived termites than in short-lived non-termite cockroaches. The extra A>G pressure is followed by coordinated shifts in synonymous nucleotide composition, codon usage, and amino acid composition. Life history can therefore travel from mutagen exposure through mtDNA spectra into the proteome. Mitochondrial genomes are archives of how a species lives, not only of who it is related to.
Source preprint: From life history to proteome via mutagenesis: an ecological footprint in genome evolution
- biorxiv2026-08-17score 68agingproteostasismetabolism
PCC1 rewrites senescent stromal ribosomes and membranes; mitochondrial-membrane genes stay high
Reanalysis of RNA-seq from bleomycin-senescent PSC27 human stromal cells treated with 50 µM procyanidin C1 (PCC1) finds 8,420 differentially expressed genes. Ribosomal genes move first, then lysosomal ones. Lipid-transport programs that fell in senescence rise after PCC1. Lysosomal-membrane, mitochondrial-membrane, cholesterol, and ion-transport programs rose in senescence and rise again after PCC1. A SASP-effector score falls; a broad Reactome SASP set does not. This is a senomorphic transcriptome, not a mitochondrial biochemistry paper.
Source preprint: PCC1 treatment reshapes ribosomal, lysosomal and membrane-lipid transcriptional programs in therapy-induced senescent human stromal cells
- medrxiv2026-09-04score 67metabolismhepatologydiet
An 8-week very-low-calorie diet drops liver fat as ketones and TCA intermediates rise
In a pilot of women with obesity and metabolic dysfunction-associated steatotic liver disease, an 8-week very-low-calorie diet cut weight about 11% and hepatic controlled-attenuation-parameter fat without changing stiffness. Ketones go up, amino acids go down, and CAP change tracks amino acids up and ketones plus tricarboxylic-acid-cycle intermediates down. A few circulating microRNAs move with CAP and HOMA-IR.
Source preprint: Very low-calorie diet reduces hepatic steatosis and remodels circulating metabolite-microRNAs networks in metabolic dysfunction-associated steatotic liver disease: A pilot study
- medrxiv2026-08-10score 67metabolismneurobiologyclinical
Neuropsychiatric long COVID serum is a lipid-and-acylcarnitine map that tracks mood, fatigue, and cortex
Patients with neuropsychiatric long COVID differ from healthy controls in serum triacylglycerides and acylcarnitines. Those metabolite shifts associate with depressive and fatigue burden and with cortical-thickness differences in multiple regions. The authors read the pattern as lipid-metabolism dysregulation and a possible deficit in mitochondrial energy production. This is a peripheral metabolome association study, not a muscle or brain respirometry.
Source preprint: Peripheral metabolic signatures in patients with neuropsychiatric long COVID syndrome
- biorxiv2026-09-03score 66immunologycancermetabolism
Stool valerate marks CAR-T dysbiosis; the fatty acid itself opens chromatin differently than butyrate
Low stool valerate at CAR-T eligibility tracks a fiber-fermenter-poor, SCFA-poor microbiome. PIM antibiotics leave CD4-skewed, AP-1-high products that predict worse survival. Ex vivo valerate, unlike butyrate or propionate, engages KLF/SP/EGR, opens KLF4, and induces AP-1 and MHC II, while propionate prefers low-mitochondrial-content states. The organelle note is that propionate commitment, not valerate's main act.
Source preprint: Microbial valerate is associated with CAR T dysbiosis and its supplementation enhances CAR T function in B-cell lymphoma
- biorxiv2026-08-13score 66cancerproteomicsmethods
Automated FFPE melanoma proteomes: regressing tumors run hotter mitochondria and quieter complement
A Tecan Fluent 780 automated deparaffinization workflow beats manual processing on 54 primary cutaneous melanomas (6,146 vs 4,941 proteins, less technical noise) while keeping global profiles comparable (8,305 proteins shared, 96.1%). In tumors with histological regression (21 vs 33), 97 proteins are up and 226 down. Enrichment says higher mitochondrial and translational activity and lower innate-immune/complement pathways in regressing lesions. Survival does not differ in this early-stage cohort. Digital pathology says morphology survives automation.
Source preprint: From Routine Pathology to Precision Oncology: Automated FFPE Tissue Processing for Large-Scale Molecular Studies
- biorxiv2026-08-09score 66mtDNAevolutionpopulation genetics
Gilded catfish split at the Rupununi Portal; mtDNA and nuclear SNPs kill the Casiquiare myth
Brachyplatystoma rousseauxii populations in the Orinoco and Amazon are genetically distinct, with no current gene flow, on nuclear microsatellites, ddRADseq, and mitochondrial DNA. A possible secondary contact left a signal in the Boa Vista sample. The split dates to the Rupununi Portal (~2.54 Ma ddRAD, ~1.31 Ma mtDNA), not the Late Miocene Vaupés Arch. The Casiquiare Canal and Japurá-Guaviare headwaters are not the connectors. Orinoco expanded; Amazon stayed demographically quieter. This is historical biogeography that uses mtDNA as a clock, not organelle physiology.
Source preprint: Historical biogeography and population genetic structure of the giant gilded catfish ( Brachyplatystoma rousseauxii ): expanding Humboldtian connectivity routes between the Orinoco and Amazon River basins
- biorxiv2026-08-17score 65apoptosismethodsstructural biology
Cell-free nanodiscs let full-length Bcl-xL, Bax, and Bak sit in a membrane where they actually work
BCL-2-family proteins toggle between cytosol and the mitochondrial outer membrane, and their membrane-embedded structures are still thin. This methods paper gives protocols to make untagged, full-length Bcl-xL, Bax, and Bak from bacterial cell-free extracts in the presence of pre-assembled lipid nanodiscs, then purify them. Bak is worked up as the example for structural and mechanistic follow-on. The product is a membrane-inserted MOM-protein reagent, not a new apoptotic pathway.
Source preprint: Production of membrane-embedded Bcl-2 proteins - Use of cell-free synthesis in continuous exchange for co-translational insertion of Bcl-2 proteins in lipid bilayer nanodiscs
- medrxiv2026-09-03score 64neurobiologyophthalmologypsychiatry
Shared genes between retina and psychiatry put mitochondria on the bipolar-disorder side
Retinal-layer genetics overlap major psychiatric disorders, most with ganglion-cell inner plexiform thickness (~60%). Pathway follow-up is disorder-specific: schizophrenia looks GABAergic and developmental; bipolar disorder looks mitochondrial with a weaker developmental component; depression looks synaptic and gene-expression. The eye is a window, and for bipolar it is an organelle window.
Source preprint: Molecular Underpinnings of Retinal Traits Shared with Major Psychiatric Disorders
- biorxiv2026-08-20score 64cytoskeletonmethods
DAAM1 builds Tpm3.2 actin at adhesions; mitochondria here are only a polymerase sink
At focal adhesions, DAAM1 formin assembles tropomyosin Tpm3.2-actin filaments, while Ena/VASP proteins polymerize α-actinin-cross-linked bundles. The authors used mitochondrial targeting of actin polymerases as a sequestration tool, not as a mitochondrial-biology experiment. Losing DAAM1 drops Tpm3.2 and impairs adhesion disassembly, copying Tpm3.2-deficient cells. Losing Ena/VASP blocks adhesion maturation and removes α-actinin. Two linear actin arrays, two polymerases. The organelle is a dump address for the tool.
Source preprint: DAAM1 formin and Ena/VASP proteins assemble functionally distinct actin filaments for focal adhesions
- biorxiv2026-08-17score 64computationalcancerproteomics
ProtInt warps cell-line proteomes toward tumors and turns down mitochondrial gene-expression proteins
ProtInt is a deep-learning integrator that aligns label-free proteomes of 771 cancer cell lines and 550 treatment-naïve tumors despite missing values. It beats batch correction and transcriptomic-integration methods at making cell-line and tumor proteomes comparable. After integration, cell-line proteomes that have been warped toward tumors show recurrent gains in immune, cell–cell communication, and ECM proteins, and losses in transcription, RNA processing, and mitochondrial gene-expression proteins. The mitochondrial sentence is a systematic adaptation signature, not a functional assay.
Source preprint: Integration of proteomic data from cell lines and tumors
- biorxiv2026-08-14score 64bioenergeticsOXPHOStheory
A theory paper: infrared photons as a Marcus-theory bias on mitochondrial electron transfer
This is a physical-framework essay, not an experiment. The authors note that built environments replaced infrared-rich daylight with narrow visible lighting, and that the solar photon-energy peak near 0.75 eV overlaps mitochondrial electron-transfer reorganization energies. In a Marcus-type picture, infrared photons could bias barrier crossing rather than donate chemical energy, and they penetrate tissue as a diffuse field. They name this “photometabolism” and offer a scaling argument that photon interception in this band tracks basal metabolic rate with body mass. No mitochondrion was illuminated in a controlled assay in the abstract.
Source preprint: Metabolism in the Solar Photon Field A physical framework for photon-assisted modulation of mitochondrial electron-transfer kinetics
- biorxiv2026-08-18score 63mtDNAmethodsentomology
Arizona Culex mitogenomes: first USA quinquefasciatus through the AT-rich control region, plus a 905-bp tarsalis insert
Long-range PCR plus PacBio HiFi yields complete, annotated mitochondrial genomes from Arizona West Nile vectors Culex quinquefasciatus (15,587 bp, first USA mitogenome through the AT-rich control region) and Culex tarsalis (16,416 bp, 905 bp longer than California and Texas references because of a control-region insertion). Phylogeny supports the species IDs. The method is aimed at pooled vector-surveillance samples. This is medical entomology infrastructure, not bioenergetics.
Source preprint: Complete mitochondrial genomes of Arizona West Nile virus vectors, Culex quinquefasciatus and Culex tarsalis
- biorxiv2026-08-11score 63cancermtDNAtherapeutics
IOMM-Lee is an NF2-wildtype, TERT-mutant Grade 3 meningioma line with catalogued mtDNA and a drug list
The widely used malignant meningioma line IOMM-Lee is confirmed NF2-wildtype with a pathogenic TERT promoter c.-124C>T variant. The authors add mtDNA variants, short doubling time (19–21 h), high colony-forming efficiency (up to 87%), relative radiosensitivity (D10 ~3.9 Gy) that ATM inhibition (AZD-1390) can worsen, and a 349-compound screen that yields 34 sub-micromolar clinical-use hits. This is a model-characterization resource, including mitochondrial genotypes, not a mitochondrial-mechanism paper.
Source preprint: ‘An NF2- wildtype malignant meningioma cell line for basic and translational science’
- biorxiv2026-08-12score 62computationalOXPHOSimmunology
PerturbLDM predicts unseen drug–dose–line transcriptomes and keeps an interferon FAO-OXPHOS program
PerturbLDM is a Tahoe-100M-pretrained latent-diffusion model that generates single-cell transcriptional responses to perturbations. On 13,942 held-out drug/dose/line combinations it beats leading methods and beats an additive marginal baseline in 95.2% of conditions. It ranks PANACEA compounds by pathway neighbors, builds a fetal-colon state more accurately than Squidiff, and in PBMCs captures six of seven interferon/antiviral programs plus an interferon-associated FAO-OXPHOS program better than scGen. The mitochondrial hook is that FAO-OXPHOS module, not a new metabolic mechanism.
Source preprint: PerturbLDM: conditional latent diffusion for modelling single-cell perturbation responses
- biorxiv2026-08-11score 62mtDNAevolutionpopulation genetics
A hybrid polyploid weevil walked north; mtDNA and SNPs say mate limitation, not a new mutation each mile
In the flightless weevil Catapionus nebulosus group, an all-female polyploid lineage has a single origin, a hybrid signal between two sexual lineages, and a rapid northern expansion. Unmated females produce fertile daughters. Sexual populations already lose effective size and diversity toward the north, south of the contact zone. Mate limitation is the favored explanation for why the parthenogen outruns its sexual relatives. Mitochondrial DNA plus genome-wide SNPs are the historical tools.
Source preprint: Walking Alone to the North: The Origin and Historical Expansion of the Polyploid Parthenogenetic Lineage in a Weevil
- biorxiv2026-09-09score 61methodstoxicologycancer
Cell Painting sees genotoxic mammary carcinogens wreck mitochondria and ER, then misses the hormone mimics
In JUMP-CP Cell Painting profiles, genotoxic mammary carcinogens shove endoplasmic reticulum, mitochondria, nucleus, and RNA compartments off their morphological baseline. Hormonally active compounds look like solvent. A guilt-by-association ranker only reaches AUC-ROC 0.63, and the authors say you will need a hormone-sensitive cell if you want endocrine disruptors.
Source preprint: Cell Painting-Based Tool for the Risk Assessment of Mammary Carcinogens and Endocrine Disruptors
- biorxiv2026-08-31score 61bioenergeticsinfectionredox biology
Phytophthora under PEG water limitation grows faster and turns alternative oxidase up
Five percent PEG-3350, a moderate water limit, speeds Phytophthora cinnamomi radial growth. A time-resolved proteome (1,097 groups) mostly falls; the few risers include thioredoxin/glutaredoxin and alternative oxidase. Adaptation looks like redox and mitochondrial metabolic regulation, not a crash stress response.
Source preprint: Osmotic adaptation rather than stress response: A time-resolved proteomic analysis of PEG-induced water limitation in Phytophthora cinnamomi
- biorxiv2026-08-21score 61agingmetabolismtoxicology
Low-dose microcystin-LR hits senescent killifish in two sexes: shared pck1 loss, divergent mitochondria-adjacent programs
Eight-month-old GRZ Nothobranchius furzeri exposed to 0.5 µg/L microcystin-LR show strongly sex-split transcriptomes (313 DEGs male, 263 female, only 27 shared). Shared space includes strong pck1 downregulation and genes of mitochondrial function, metabolism, ECM, and genome maintenance. Males remodel sarcomere/contractile programs; females remodel vitellogenin/zona pellucida and metabolic reproduction. Aging plus a bloom toxin is not one pathway.
Source preprint: Low-Dose Microcystin-LR Elicits Sex-Dimorphic Transcriptomic Responses in Senescent Nothobranchius furzeri: Implications for Cyanotoxin Vulnerability in Aging Vertebrates
- biorxiv2026-08-11score 61biomaterialswound healingtherapeutics
A spermidine-crosslinked DNA hydrogel clots like a NET and advertises mitochondrial protection as a side brief
A DNA hydrogel meant to mimic neutrophil extracellular traps is crosslinked with spermidine, a small molecule the authors credit with autophagy, cardioprotection, anti-inflammation, antioxidant activity, and mitochondria protection. The DNA net recruits platelets and red cells for rapid hemostasis; as it degrades, spermidine is released into the wound. In mice the gel clots and speeds closure. The mitochondrial claim is a listed property of the crosslinker, not a wound-bed respirometry result.
Source preprint: Bioactive Spermidine-Crosslinked DNA Hydrogel for rapid homeostasis and accelerated wound healing
- biorxiv2026-08-13score 60mtDNAmethodscomputational
pastForward finishes ancient libraries and screens them for eukaryotic mitochondria at scale
pastForward is a Snakemake pipeline from raw ancient/historical reads to damage-rescaled BAMs, with reports on endogenous content, complexity, and coverage. It maps to multiple references (host plus endosymbiont, COI). Two new tools: ECMSD screens libraries against a mitochondrial reference database for eukaryotic DNA; REVEAL quantifies copy-number of TEs and duplications. Case studies: AMY2B copy number rises across dog domestication including Neolithic samples; the TE opus invades D. melanogaster after the 1800s and is present from 1933. Mitochondria here are a taxonomic detector, not a physiology target.
Source preprint: pastForward: a Snakemake pipeline for ancient and historical DNA with eukaryote-wide taxonomic screening and tracking of copy-number variation
- biorxiv2026-08-10score 60immunologychromatindevelopment
MLLT1’s YEATS reader is required for B lymphopoiesis and lands on a mitochondrial-function gene set
Conditional Mllt1 deletion collapses early B development: fewer marrow progenitors, splenic transitional B cells, and blood B cells, in vivo and cell-intrinsically in vitro. Direct targets include Il7r, Ebf1, and Pax5. Enrichment analyses of deficient cells move B-development, signaling, DNA replication, and mitochondrial-function programs. Wild-type MLLT1 rescues; YEATS-domain mutants that cannot read chromatin or bind RNA do not. A leukemia translocation partner is a normal B-cell maintenance gene with a mitochondrial-function transcriptional echo.
Source preprint: The chromatin reader protein MLLT1 is critical to maintain normal B lymphopoiesis
- biorxiv2026-08-09score 60mtDNAevolutionconservation
White-bellied heron genomes: sister to purple heron, chronically small Ne, mitonuclear discordance deeper in the family
The first high-quality Ardea insignis genome (Nanopore plus Illumina), with fewer than 60 wild birds left, shows the species as sister to purple heron, with moderate mitonuclear discordance among deeper ardeids. Heterozygosity is extremely low and runs of homozygosity are extensive versus great blue heron, but short/intermediate ROH plus PSMC say the tiny Ne is old, not only a last-century crash. The two sampled birds differ in long ROH, so recent inbreeding is uneven. The conservation problem is limited adaptive potential after chronic rarity. Mitochondria contribute a phylogeny that is not perfectly nuclear.
Source preprint: The fate of a dynasty: Population genomics uncovers the demographic history of Ardea insignis , one of the rarest bird species in the world
- biorxiv2026-09-16score 58mtDNAconservationpopulation genetics
Saimaa ringed seals keep 5% of mitochondrial diversity and about 1% of Y-chromosome diversity
The endangered Saimaa ringed seal already looked genetically poor on mitochondrial DNA and autosomes. A chromosome-level reference that includes a curated Y chromosome, plus resequencing of 80 animals, now says the paternal lineage is worse: relative to other ringed seals the population retains about 5 percent of mitochondrial diversity and about 1 percent of Y-chromosomal diversity. Both the Y and the mitochondrion are monophyletic against Baltic, Ladoga, and Arctic ringed seals.
Source preprint: A chromosome-level reference genome assembly reveals extreme loss of Y-chromosomal diversity in the Saimaa ringed seal (Pusa saimensis)
- biorxiv2026-09-10score 58mtDNApopulation geneticsphylogeography
A rare Siberian mitochondrial lineage in Nilgiri Kurumba dates Holocene maternal gene flow into South India
Complete mitochondrial genomes from Toda, Kota, and Kurumba tribes in the Nilgiri Hills show deep founder effects and one rare surprise: haplogroup C4a2c1 in Kurumba, a North Asian/Siberian maternal line that Bayesian dates put into the subcontinent about 7,000 years ago. The organelle genome is the clock; the story is Holocene contact, then isolation.
Source preprint: Holocene North Asian gene flow and cryptic substructure in the genome history of Nilgiri tribes
- biorxiv2026-08-17score 58metabolismimmunologydevelopment
On a rich diet, fly microbiome timing barely rewires adults; a handful of mitochondrial genes stay marked
Drosophila colonized as newly hatched larvae versus newly eclosed adults, all on a rich diet, show only modest adult transcriptional shifts versus axenic flies (~25–200 DEGs, mostly immune up). Only about 10 genes stay differentially expressed if bacteria are given to adult-axenic flies too late to erase the larval-timing mark. That persistent set includes mitochondrial genes, Adh, and a putative secreted neuropeptide. Development on rich food is mostly robust to when microbes arrive; a thin metabolic/mitochondrial residue may not be.
Source preprint: Role of Early-Life Microbiome Colonization in Physiological Development of Drosophila melanogaster
- biorxiv2026-08-14score 58mtDNAevolutionsymbiosis
Pineus strobi adds a 25.3 kb mitogenome and shows adelgid chromosomes barely shuffled for 90 million years
The first Pineus chromosome-scale genome (pine bark adelgid) keeps major linkage groups with Adelges across ~90 million years. Grape phylloxera’s five chromosomes still correspond, with limited fusions/fissions. Aphid-style interautosomal chaos is not an Aphidomorpha-wide rule. The authors also recover a complete 25.3 kb mitochondrial genome with expanded repeat-rich noncoding DNA, circular genomes of the nutritional symbionts Annandia and Hartigia pinicola (syntenic with Pineus similis), and the first complete adelgid Wolbachia. mtDNA is one of several completed circles.
Source preprint: The chromosome-scale genome of the pine bark adelgid reveals conserved macrosynteny across Adelgidae
- biorxiv2026-09-06score 57methodsimmunology
10X and Parse scRNA-seq disagree on mitochondrial gene capture and on TEMRA killer genes
A head-to-head of 10X Genomics versus Parse on PBMCs and CD8 TEMRA cells finds platform-specific mitochondrial and ribosomal capture, a 10X bias for short genes, a Parse bias for long transcripts, and under-calling of GNLY, PRF1, and GZMB on Parse. Cell-type stories, including mitochondrial ones, will move with the kit.
Source preprint: Systematic Comparison of 10X Genomics and Parse Single Cell RNA Technologies across PBMC and CD8 + TEMRA Cells
- biorxiv2026-08-17score 57mtDNAmethodsecology
COI hybridization capture pulls ~450 freshwater invertebrate genera from creek eDNA
Custom RNA baits for regional freshwater arthropod, annelid, and mollusc mitochondrial COI sequences enrich environmental DNA ~1,760-fold over shotgun libraries and build ~400 bp Folmer-region contigs. Along 63 km of Boulder Creek (18 sites, 1,500 m elevation), about 450 genera across 8 phyla appear; richness averages 56 genera per site and tracks a known conventional bioassessment pattern. This is mitochondrial barcode capture as a bioassessment tool.
Source preprint: Targeted hybridization capture enables comprehensive detection of freshwater bioassessment invertebrates from environmental DNA
- biorxiv2026-08-11score 57mtDNAevolutionphylogenomics
Xanthophyte phylogenomics: four origins of simple multicellularity, with mitochondria agreeing on the tree
A 680-gene nuclear tree from 18 xanthophytes (17 new transcriptomes), plus matching plastid (141 genes, 33 species) and mitochondrial (31 genes, 33 species) topologies, rewrites yellow-green algal orders and families. Ancestral reconstruction finds at least four independent unicellular-to-simple-multicellular transitions, each paired with a shift from many autospore-type propagules to single monospore/akinete-type ones; reversions bring autospores back. Mitochondria are a concordant phylogenetic dataset, not a physiology story.
Source preprint: Evolution of multicellularity and reproductive strategies in yellow-green algae (Xanthophyceae, Heterokontophyta)
- biorxiv2026-08-09score 57mtDNAmethodsinvasion biology
Pasture mealybug COI: a 10% mitochondrial split, and one haplotype for the US invasion
The first COI barcode for Heliococcus summervillei reveals ~10.2% mitochondrial divergence between Type A and Type B. All invasive-range samples (United States, Australia, Pakistan, Caribbean) share one haplotype from a recent invasion; Barbados holds two closely related, historically stable haplotypes. The barcode is a regulatory ID tool for a grass-killing mealybug. Mitochondria are the diagnostic molecule.
Source preprint: Development of the First Cytochrome Oxidase I Barcode and Evidence for a Single Haplotype Associated with the Recent United States Invasion of the Pasture Mealybug Heliococcus summervillei (Pseudococcidae, Hemiptera)
- biorxiv2026-08-11score 56mtDNAevolutionpathogen genomics
Colletotrichum cereale’s first chromosome-scale genome includes a mitochondrion and three huge accessory chromosomes
A 58.01 Mb Nanopore/Hi-C/Illumina assembly of C. cereale isolate 6B yields 13 chromosome-scale scaffolds plus a mitochondrial genome (N50 5.44 Mb, 98.6% BUSCO). Three AT-rich, gene-poor accessory chromosomes (2.71, 1.86, 1.36 Mb) are the first chromosome-scale accessory set in this grass anthracnose fungus and among the largest in the genus. They carry predicted effectors, CAZymes, and BGCs and show wild presence-absence variation across isolates. Core genomes still split clades A and B (ANI ~92–99.9%). Mitochondria are an assembled circle in a pathogen genome paper.
Source preprint: A chromosome-scale genome of Colletotrichum cereale reveals a large, dynamic accessory genome within a deeply structured species
- biorxiv2026-09-09score 55mtDNAevolutionecology
Brine-fly mitochondrial lineages sort with the salinity of the water they actually use
Ephydra brine flies in San Francisco Bay salt ponds pick habitats by salinity, and a single-locus mitochondrial genealogy spanning about 40 years and distant sites says those salinity envelopes are not independent of evolutionary relatedness. Extremophile ecology here is partly a mitochondrial-lineage map.
Source preprint: Salinity is associated with habitat use and mitochondrial lineage diversity in halophilic Ephydra flies (Diptera: Ephydridae)
- biorxiv2026-08-15score 55mtDNAmethodsentomology
SDA-500 is a new Anopheles stephensi cell line, stamped male by karyotype and COI
An embryo-derived A. stephensi (SDA-500) line grows in vitro, is identified by mitochondrial COI barcoding, and is at least partly male (diploid karyotype with a Y). TransIT-PRO transfects better than Lipofectamine reagents. Among tested promoters, Anopheles gambiae polyubiquitin is the strongest, most consistent driver in a dual-luciferase assay. The line is a functional-genomics chassis for an urban malaria vector. Mitochondria are the species barcode.
Source preprint: Development and validation of an SDA-500 Anopheles stephensi cell line for molecular studies
- biorxiv2026-08-11score 55mtDNAecologypopulation genetics
Pitcher-plant mites and midges track the host landscape, not each other; chloroplast and COI disagree in useful ways
Across Darlingtonia californica’s patchy range, the plant’s nuclear diversity falls toward the margins (central-marginal) while chloroplast structure is weaker and mainly splits northern Oregon Coast plants, a cytonuclear discordance consistent with seed movement or chloroplast capture. Circuit-theoretic connectivity from an ecological niche model predicts plant gene flow; landscape resistance explains plant and mite differentiation beyond distance. Both the midge and the mite are spatially congruent with the plant, not with each other, so they are not co-dispersing. Mitochondrial COI is the arthropod marker; chloroplast is the plant organelle marker.
Source preprint: Connectivity and dispersal mode shape the landscape genetics of a carnivorous pitcher plant-arthropod metacommunity
- biorxiv2026-09-08score 54immunologymetabolismosteoarthritis
Osteoarthritic synovial fibroblasts wreck cartilage after TLR ligation, with barely a dent in mitochondrial respiration
Human osteoarthritis synovial fibroblasts are wired for Toll-like receptors. Hit TLR1/2, 4, 5, or 2/6 and they pour out IL-6, IL-8, G-CSF, MMP3, and MMP10 and then teach autologous chondrocyte spheroids to become inflammatory, catabolic, and small. Mitochondrial respiration, which they measured, barely moves. The organelle is a negative control here, not the driver.
Source preprint: TLR-mediated activation of synovial fibroblasts from osteoarthritis patients promotes chondrocyte dysfunction
- biorxiv2026-09-04score 54mtDNAevolutionspeciation
African giant shrews show mitonuclear discordance from repeated hybridization, not one messy tree
Genome-wide ddRAD plus mitochondrial data across sub-Saharan Crocidura olivieri reveal extensive mitonuclear discordance caused by repeated introgression, three major lineages, four introgression events, and five geographically structured lineages still exchanging genes. Mitochondria here are the discordant tape, not the physiology.
Source preprint: Incipient speciation, rapid expansion and repeated introgressive hybridization in an African Giant Shrew ( Crocidura olivieri )
- biorxiv2026-08-11score 52mtDNAinfectionpublic health
Belitung macaques carry four zoonotic Plasmodium species; complete mitochondria pin local P. knowlesi
Of 163 long-tailed macaques already known as a Brugia malayi reservoir in Belitung, 79.8% are pan-Plasmodium qPCR positive: P. inui 41.7%, P. knowlesi 38.7%, P. coatneyi 24.5%, P. cynomolgi 13.5%, with 37% mixed. 20 of 22 filaria-positive animals also carry at least one Plasmodium. Complete mitochondrial genomes from nine apparent mono-infections confirm seven P. knowlesi plus one P. inui and one P. coatneyi; Belitung P. knowlesi mitochondria cluster with human and monkey samples from Thailand, Malaysia, and Indonesia. A district called malaria-free still has a zoonotic mitochondrial reservoir.
Source preprint: Detection of Plasmodium infections in macaques from areas endemic for brugian filariasis in Belitung District, Indonesia
- biorxiv2026-09-04score 50mtDNApopulation geneticsconservation
Central European wolves now overlap, and mitochondrial haplotypes help name who moved where
A five-year Central European wolf campaign uses mitochondrial haplotypes plus microsatellites to show three ancestries (Central European/Baltic, Carpathian, Alpine) now sit in mosaic sympatry, with asymmetric immigration. The organelle is a lineage tag, not a respiratory-chain result.
Source preprint: Wolf microevolution in the melting pot: range expansion, population sympatry, dynamic mosaic admixture zone and asymmetric gene flow
- medrxiv2026-09-03score 46biomarkersneurobiology
A calpain-cut GFAP neoepitope beats total GFAP for Veteran MCI and Alzheimer triage
Across a Veteran TBI-MCI-Alzheimer continuum, a calpain-cleaved GFAP neoepitope (neoGFAP) outperforms total GFAP for separating MCI plus Alzheimer from non-Alzheimer subjects, especially after a plasma p-tau217 and amyloid-beta-42 gate. This is astroglial injury, not a mitochondrial paper.
Source preprint: Proteoform-resolved neoGFAP ™ as a diagnostic and prognostic biomarker across the TBI–MCI–AD continuum in Veterans
- biorxiv2026-09-04score 44neurobiologyimmunology
Chronic stress sex-splits brain-resident T cells into male type-1 and female type-17 programs
Unpredictable chronic mild stress makes both sexes look depressed, then diverges: females lose regional synapses, males lose hippocampal neurons. Brain-resident lymphocytes carry the cytokine split. Females enrich gamma-delta type-2/17 and inflammasome genes; males enrich alpha-beta and NKT type-1, CXCR3, IL27RA, and IFNgamma after stress. Mitochondria are not the measured object.
Source preprint: Chronic stress promotes sex-divergent Type 1, 2 and 17 responses in brain resident lymphocytes
- biorxiv2026-09-03score 41mtDNAecology
Smoke-fly larvae finally turn up in burnt soil, identified by mitochondrial COI
Microsania smoke flies swarm at Finnish prescribed burns; larvae in burnt soil barcode as Microsania mitochondrial COI, including the first larval description of M. straeleni. The organelle is a species ID tool.
Source preprint: Pyrophilic smoke flies (Diptera: Platypezidae: Microsaniinae) from prescribed burnings in boreal Finland: occurrence and behaviour of adult flies and first observations of immature stages
- biorxiv2026-09-03score 40mtDNAmethods
A demineralization protocol pulls mitochondrial cytochrome b from rotten cetacean bone
Nine environmentally degraded cetacean bones yield 7.3-57.1 ng/uL DNA after EDTA/N-lauroylsarcosine/proteinase K demineralization and silica cleanup. Mitochondrial cytochrome b PCR works in all; five sequences call Balaenoptera physalus. The organelle genome is the ID tool.
Source preprint: Optimizing DNA extraction from environmentally degraded bone samples for molecular identification of cetacean species