biorxiv2026-10-28score 92
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.
