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Mitochondria importance articles
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25 of 176 articles · updated 2026-09-18T14:04Z
- 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
- biorxiv2026-09-03score 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
- biorxiv2026-09-08score 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
- biorxiv2026-08-20score 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 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
- biorxiv2026-08-19score 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
- biorxiv2026-08-17score 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
- biorxiv2026-08-26score 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
- biorxiv2026-08-14score 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
- 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
- biorxiv2026-09-03score 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
- biorxiv2026-09-04score 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 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
- biorxiv2026-08-16score 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
- biorxiv2026-08-14score 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
- biorxiv2026-09-03score 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
- biorxiv2026-08-12score 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
- biorxiv2026-08-10score 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
- biorxiv2026-08-17score 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
- biorxiv2026-09-06score 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
- biorxiv2026-09-08score 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 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