Abstract: The oligomycin-sensitivity conferring protein (OSCP) of the mitochondrial FOF1 ATP synthase has long been recognized to be essential for the coupling of proton transport to ATP synthesis. Located on top of the catalytic F1 sector, it makes stable contacts with both F1 and the peripheral stalk, ensuring the structural and functional coupling between FO and F1, which is disrupted by the antibiotic, oligomycin. Recent data have established that OSCP is the binding target of cyclophilin (CyP) D, a well-characterized inducer of the mitochondrial permeability transition pore (PTP), whose opening can precipitate cell death. CyPD binding affects ATP synthase activity, and most importantly, it decreases the threshold matrix Ca2+ required for PTP opening, in striking analogy with benzodiazepine 423, an apoptosis-inducing agent that also binds OSCP. These findings are consistent with the demonstration that dimers of ATP synthase generate Ca2+-dependent currents with features indistinguishable from those of the PTP and suggest that ATP synthase is directly involved in PTP formation, although the underlying mechanism remains to be established. In this scenario, OSCP appears to play a fundamental role, sensing the signal(s) that switches the enzyme of life in a channel able to precipitate cell death.
Keywords: mitochondria; oligomycin-sensitivity conferring protein (OSCP); cyclophilin D (CyPD); FOF1 ATP synthase dimer; permeability transition pore (PTP)
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Antoniel, M.; Giorgio, V.; Fogolari, F.; Glick, G.D.; Bernardi, P.; Lippe, G. The Oligomycin-Sensitivity Conferring Protein of Mitochondrial ATP Synthase: Emerging New Roles in Mitochondrial Pathophysiology. Int. J. Mol. Sci. 2014, 15, 7513-7536.
Antoniel M, Giorgio V, Fogolari F, Glick GD, Bernardi P, Lippe G. The Oligomycin-Sensitivity Conferring Protein of Mitochondrial ATP Synthase: Emerging New Roles in Mitochondrial Pathophysiology. International Journal of Molecular Sciences. 2014; 15(5):7513-7536.
Antoniel, Manuela; Giorgio, Valentina; Fogolari, Federico; Glick, Gary D.; Bernardi, Paolo; Lippe, Giovanna. 2014. "The Oligomycin-Sensitivity Conferring Protein of Mitochondrial ATP Synthase: Emerging New Roles in Mitochondrial Pathophysiology." Int. J. Mol. Sci. 15, no. 5: 7513-7536.