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. 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 targ...

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Published in:British journal of pharmacology Vol. 176; no. 22; pp. 4247 - 4257
Main Authors: Giorgio, Valentina, Fogolari, Federico, Lippe, Giovanna, Bernardi, Paolo
Format: Journal Article
Language:English
Published: England Blackwell Publishing Ltd 01.11.2019
John Wiley and Sons Inc
Subjects:
Animals
ATP synthase
Calcium channels
Calcium conductance
Cell death
Cyclosporin A
Enzymes
Humans
Membrane permeability
Mitochondrial Membrane Transport Proteins
Mitochondrial Permeability Transition Pore
Mitochondrial Proton-Translocating ATPases - chemistry
Mitochondrial Proton-Translocating ATPases - metabolism
Oligomycin
Protein Subunits - chemistry
Protein Subunits - metabolism
Review
Themed Section: Review
ISSN:0007-1188, 1476-5381, 1476-5381
Online Access:Get full text
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Summary: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 FOF1 (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 Ca2+‐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
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ISSN:0007-1188
1476-5381
1476-5381
DOI:10.1111/bph.14513