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.
