Archive · 2026-W44

Mito.news 2026-W44

5 articles. Each URL is the original /articles/{id} path.

• biorxiv2026-10-23score 91

  ANO6 scaffolds ER-mitochondria contacts that hide peroxidizable lipids from ferroptosis

  Yang, Yan and colleagues report that ANO6, better known as a plasma-membrane phospholipid scramblase, works at mitochondria-associated ER membranes as a conformational scaffold. It assembles a vimentin-ANO6-VAPB-PTPIP51 tether that tightens ER-mitochondria coupling and routes polyunsaturated phospholipids into cytoplasmic lipid droplets. That spatial sequestration shields bilayer lipids from ferroptotic peroxidation in chemoresistant breast cancer. Niclosamide or scaffold-dead ANO6 (D703R) collapses the compartment and resensitizes tumors to ferroptosis, including with GPX4 inhibition. The abstract does not name a labile Fe2+ pool or an iron-sulfur cluster. Ferroptosis here is iron-dependent lipid peroxidation of PUFA phospholipids, inferred from the death mode and from RSL3, not from a measured metal site.

• medrxiv2026-10-19score 89

  Biallelic UQCC1 variants are a cause of mitochondrial complex III deficiency

  Smith, Taylor and colleagues assign UQCC1, a complex III assembly factor not previously tied to human disease, as a recessive cause of early-onset mitochondrial disease with lactic acidosis. Nine people from eight families carry biallelic UQCC1 variants. Patient fibroblasts lose UQCC1 and its partner UQCC2, lose CIII2 on BN-PAGE and proteomics, delay insertion of new CIII subunits into native assemblies, and fail respiratory supercomplexes. Lentiviral UQCC1 restores protein and CIII2 activity. Complex III (ubiquinol:cytochrome c oxidoreductase) moves electrons from ubiquinol (QH2) to cytochrome c, then to Complex IV. Its catalytic metal sites are heme bL, heme bH, heme c1, and the Rieske [2Fe-2S] cluster. This abstract shows assembly and activity loss. It does not show which cofactor insertion step UQCC1 fails, and it does not report cluster spectroscopy.

• biorxiv2026-10-21score 87

  PARP1/2 ADP-ribosylation, not tankyrase, is what impairs trophoblast mitochondrial respiration in TNF-alpha preeclampsia

  Nik-Akhtar, Bainbridge and colleagues place inflammation-mediated preeclampsia on a PARP1/2-NAD+ axis rather than a tankyrase axis. TNF-alpha drives a PARP1-associated ~120 kDa mono- and poly-ADP-ribosylation signal in HTR-8/SVneo trophoblasts. Olaparib suppresses that signal and restores basal respiration, maximal respiration, ATP production, and spare capacity. The tankyrase inhibitor XAV939 does neither. OXPHOS subunit abundance, 4-hydroxynonenal, viability, and migration are unchanged at 24 hours, so this is a bioenergetic lesion without subunit loss and without a measured lipid-peroxidation increase. The named redox couple is NAD+/NADH: PARP consumes NAD+ to ADP-ribosylate proteins. 4-HNE is the lipid-aldehyde they measured and it did not move.

• biorxiv2026-10-28score 85

  NDUFA13 lysine-7 acetylation is the switch from OXPHOS failure to cristae collapse in heart failure

  Nan, Yang, Liu, He and colleagues identify acetylation of the Complex I accessory subunit NDUFA13 at lysine 7 as the sensor that turns OXPHOS inhibition into cristae disintegration. Hyperacetylated NDUFA13 compacts, moves toward the intermembrane space, binds PHB2, displaces PHB1, and takes apart prohibitin scaffolds. The acetylation mimic K7Q fragments cristae in cells. Cardiomyocyte-specific K7Q knock-in mice die faster under pressure overload, lose cristae, slow the TCA cycle and fatty acid oxidation, and selectively deplete polyunsaturated cardiolipins. NDUFA13 is not an Fe-S subunit. Complex I's N-module carries Fe-S clusters; this abstract does not name them or a couple at K7. The chemistry on the residue is lysine acetylation, reversed in principle by deacetylation. The membrane chemistry that fails downstream is polyunsaturated cardiolipin.

• biorxiv2026-10-12score 83

  Alexander disease astrocytes uncouple the glycerol-3-phosphate shuttle to keep cytosolic NAD+ when the electron transport chain fails

  van Gelder, Hol, Burgering and colleagues separate GFAP dose from the Alexander disease mutation R239C with single-cell proteomics. High wild-type GFAP starts to look like R239C, so accumulation matters, but the mutant specifically raises mitochondrial antioxidant enzymes and retunes the proteasome toward ATP- and ubiquitin-independent disposal of oxidized proteins. Patient cortical organoids add nuclear-encoded mitochondrial proteins and respiratory assembly factors without a matching rise in mitochondrially encoded subunits, which they read as impaired electron transport chain assembly. AxD cells then drop oxygen consumption, raise glycolysis, lean on the cytosolic arm of the glycerol-3-phosphate shuttle, and store triacylglycerides. The named couple is NAD+/NADH: partial G3P-shuttle uncoupling regenerates cytosolic NAD+ so glycolysis can run without sending those reducing equivalents fully into the Q pool. The abstract does not name GPD2, FAD, or which respiratory complex fails assembly.