OSCP subunit of mitochondrial ATP synthase: role in regulation of enzyme function and of its transition to a pore
| Autor: | Federico Fogolari, Giovanna Lippe, Paolo Bernardi, Valentina Giorgio |
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| Přispěvatelé: | Giorgio V., Fogolari F., Lippe G., Bernardi P. |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Conformational change Mitochondrial Proton-Translocating ATPase Oligomycin OSCP subunit Protein subunit Mitochondrial Membrane Transport Proteins Themed Section: Review Articles F-ATP synthase 03 medical and health sciences chemistry.chemical_compound Mitochondrial membrane transport protein 0302 clinical medicine Cyclosporin a Animals Humans Inner mitochondrial membrane Pharmacology permeability transition pore biology ATP synthase Animal Mitochondrial Permeability Transition Pore Chemistry Mitochondrial Membrane Transport Protein Mitochondrial Proton-Translocating ATPases mitochondria F-ATP synthase OSCP subunit permeability transition pore Cell biology mitochondria Protein Subunits 030104 developmental biology Mitochondrial permeability transition pore biology.protein 030217 neurology & neurosurgery Human |
| Zdroj: | Br J Pharmacol |
| Popis: | 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 F(O)F(1) (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 |
| Databáze: | OpenAIRE |
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