An NADH-controlled gatekeeper of ATP synthase

Although mechanistic understanding of ATP production is very well established, critical aspects surrounding its substrate supply logistics are poorly understood.

Combining crosslinking mass spectrometry, biochemistry, and structural and cellular approaches, the researchers identify an NADH dependent interaction between the mitochondrial proteins mitochondrial apoptosis-inducing factor 1 (AIFM1) and adenylate kinase 2 (AK2) as gatekeeper of ATP synthase.

Disruption of AIFM1/AK2 association impedes the metabolic rates and nutrient availability. 

Thus, the researchers show that AIFM1 as a cellular NADH sensor, placing AK2 next to the OXPHOS complexes for local ADP regeneration as the substrate for ATP synthesis.

https://www.cell.com/molecular-cell/fulltext/S1097-2765(25)00507-6

https://sciencemission.com/NADH-controlled-gatekeeper-of-ATP-synthase