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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.
22 of 176 articles · updated 2026-09-18T14:04Z
- 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
- biorxiv2026-08-12score 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
- biorxiv2026-08-11score 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
- biorxiv2026-08-17score 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
- biorxiv2026-09-06score 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
- biorxiv2026-08-19score 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
- medrxiv2026-09-09score 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
- biorxiv2026-08-15score 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
- biorxiv2026-09-10score 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
- biorxiv2026-09-08score 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
- biorxiv2026-09-09score 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
- 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 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
- biorxiv2026-09-03score 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
- biorxiv2026-08-17score 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
- biorxiv2026-08-11score 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’
- biorxiv2026-09-09score 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