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NAD+ mitochondria briefs

2 importance briefs tagged NAD+, including the current week and the archive.

• biorxiv2026-10-21score 93

  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.

• biorxiv2026-10-12score 91

  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.

Also: redox biology · computational · metabolism · therapeutics · structural biology · immunology · aging · neurobiology