The Oligomycin-Sensitivity Conferring Protein of Mitochondrial ATP Synthase: Emerging New Roles in Mitochondrial Pathophysiology

摘要: The oligomycin-sensitivity conferring protein (OSCP) of the mitochondrial FOF1 ATP synthase has long been recognized to be essential for coupling proton transport synthesis. Located on top catalytic F1 sector, it makes stable contacts with both and peripheral stalk, ensuring structural functional between FO F1, which is disrupted by antibiotic, oligomycin. Recent data have established that OSCP binding target cyclophilin (CyP) D, a well-characterized inducer permeability transition pore (PTP), whose opening can precipitate cell death. CyPD affects activity, most importantly, decreases threshold matrix Ca2+ required PTP opening, in striking analogy benzodiazepine 423, an apoptosis-inducing agent also binds OSCP. These findings are consistent demonstration dimers generate Ca2+-dependent currents features indistinguishable from those suggest directly involved formation, although underlying mechanism remains established. In this scenario, appears play fundamental role, sensing signal(s) switches enzyme life channel able