Acetylation of NDUFA13 at K7 Senses OXPHOS Dysfunction to Disrupt Prohibitin Scaffolds and Drive Cristae Remodelling in Heart Failure

Acetylation of mitochondrial complex I subunit NDUFA13 at lysine 7 (K7) links OXPHOS inhibition to prohibitin scaffold disruption and cristae remodelling in heart failure models.

• Why it matters: Cristae disintegration is a hallmark of heart failure, but the mechanism connecting OXPHOS dysfunction to structural collapse is unclear.
• What they did: OXPHOS inhibition increased NDUFA13-K7 hyperacetylation, which compacted and translocated NDUFA13 to the intermembrane space and competitively engaged PHB2 to disassemble prohibitin scaffolds.
• The result: The acetylation-mimetic NDUFA13-K7Q caused cristae fragmentation in vitro, and cardiomyocyte-specific K7Q knock-in mice showed accelerated mortality and cristae loss under pressure overload with impaired TCA flux, defective fatty acid oxidation, and selective depletion of polyunsaturated cardiolipins.