The oligomycin axis of mitochondrial ATP synthase: OSCP and the proton channel

Oligomycin has long been known as an inhibitor of mitochondrial ATP synthas e, putatively binding the F-o subunits 9 and 6 that contribute to proton ch annel function of the complex. As its name implies, OSCP is the oligomycin sensitivity-conferring protein necessary for the intact enzyme complex to d isplay sensitivity to oligomycin. Recent advances concerning the structure and mechanism of mitochondrial ATP synthase have led to OSCP now being cons idered a component of the peripheral stator stalk rather than a central sta lk component. How OSCP confers oligomycin sensitivity on the enzyme is unkn own, but probably reflects important protein-protein interactions made with in the assembled complex and transmitted down the stator stalk, thereby inf luencing proton channel function. We review here our studies directed towar d establishing the stoichiometry, assembly, and function of OSCP in the con text of knowledge of the organization of the stator stalk and the proton ch annel.