OSCP subunit of mitochondrial ATP synthase: role in regulation of enzyme function and of its transition to a pore. (28th November 2018)

• Record Type: Journal Article
• Authors: Giorgio, Valentina; Fogolari, Federico; Lippe, Giovanna; Bernardi, Paolo
• Is Part Of: British journal of pharmacology. Volume 176:Number 22(2019)
• Page Start: 4247
• Page End: 4257
• Publication Date: 2018-11-28
• Subjects: Pharmacology -- Periodicals; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/bph.14513
• Languages: English
• ISSNs: 0007-1188

Abstract

Abstract : The permeability transition pore (PTP) is a latent, high‐conductance channel of the inner mitochondrial membrane. When activated, it plays a key role in cell death and therefore in several diseases. The investigation of the PTP took an unexpected turn after the discovery that cyclophilin D (the target of the PTP inhibitory effect of cyclosporin A) binds to FO F1 (F)‐ATP synthase, thus inhibiting its catalytic activity by about 30%. This observation was followed by the demonstration that binding occurs at a particular subunit of the enzyme, the oligomycin sensitivity conferral protein (OSCP), and that F‐ATP synthase can form Ca 2+ ‐activated, high‐conductance channels with features matching those of the PTP, suggesting that the latter originates from a conformational change in F‐ATP synthase. This review is specifically focused on the OSCP subunit of F‐ATP synthase, whose unique features make it a potential pharmacological target both for modulation of F‐ATP synthase and its transition to a pore. Linked Articles: This article is part of a themed section on Mitochondrial Pharmacology: Featured Mechanisms and Approaches for Therapy Translation. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.22/issuetoc