OSCP subunit of mitochondrial ATP synthase: role in regulation of enzyme function and of its transition to a pore

The permeability transition pore (PTP) is a latent, high-conductance channel of the inner mitochondrial membrane. Whenactivated, it plays a key role in cell death and therefore in several diseases. The investigation of the PTP took an unexpected turnafter the discovery that cyclophilin D (the target of the PTP inhibitory effect of cyclosporin A) binds to FOF1(F)-ATP synthase, thusinhibiting its catalytic activity by about 30%. This observation was followed by the demonstration that binding occurs at aparticular subunit of the enzyme, the oligomycin sensitivity conferral protein (OSCP), and that F-ATP synthase can formCa2+-activated, high-conductance channels with features matching those of the PTP, suggesting that the latter originates from aconformational change in F-ATP synthase. This review is specifically focused on the OSCP subunit of F-ATP synthase, whoseunique features make it a potential pharmacological target both for modulation of F-ATP synthase and its transition to a pore