Free for human readers
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.
43 of 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
- biorxiv2026-08-26score 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
- biorxiv2026-08-13score 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
- biorxiv2026-08-12score 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
- biorxiv2026-09-07score 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
- biorxiv2026-08-20score 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
- biorxiv2026-09-07score 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
- biorxiv2026-08-11score 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
- biorxiv2026-09-03score 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
- biorxiv2026-08-20score 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
- biorxiv2026-08-17score 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
- 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
- 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
- biorxiv2026-08-19score 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
- 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
- biorxiv2026-08-13score 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
- biorxiv2026-09-10score 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
- biorxiv2026-08-26score 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
- 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
- biorxiv2026-08-19score 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
- 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
- biorxiv2026-09-08score 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
- biorxiv2026-09-09score 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
- biorxiv2026-08-13score 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
- 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
- biorxiv2026-09-03score 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
- biorxiv2026-08-25score 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
- biorxiv2026-08-19score 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 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
- biorxiv2026-08-11score 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’
- biorxiv2026-08-11score 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