Extrinsic conditions influence the self-association and structure of IF 1 , the regulatory protein of mitochondrial ATP synthase

Significance Adenosine triphosphate (ATP), the fuel of biology, is produced by a molecular machine with a rotary action. Inside the mitochondria of eukaryotic cells, rotation is driven by a proton-motive force across the inner membranes of the organelle generated by oxidation of sugars and fats in food. Under anoxic conditions, the rotary machine hydrolyzes ATP and reverses rotation. This wastage is prevented by an intrinsically disordered region of the inhibitor protein, IF 1 , which inserts itself in the machine and stops reverse rotation. The inhibitory activity of IF 1 is regulated by self-association, which is influenced by pH and ion-types, providing a potential molecular mechanism for the modulation of ATPase activity by cellular physiology via this solution-responsive, self-associating protein.