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Formation of High-Conductive C Subunit Channels upon Interaction with Cyclophilin D

The c subunit of the ATP synthase is an inner mitochondrial membrane (IMM) protein. Besides its role as the main component of the rotor of the ATP synthase, c subunit from mammalian mitochondria exhibits ion channel activity. In particular, c subunit may be involved in one of the pathways leading to...

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Autores principales: Amodeo, Giuseppe Federico, Krilyuk, Natalya, Pavlov, Evgeny V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538490/
https://www.ncbi.nlm.nih.gov/pubmed/34681682
http://dx.doi.org/10.3390/ijms222011022
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author Amodeo, Giuseppe Federico
Krilyuk, Natalya
Pavlov, Evgeny V.
author_facet Amodeo, Giuseppe Federico
Krilyuk, Natalya
Pavlov, Evgeny V.
author_sort Amodeo, Giuseppe Federico
collection PubMed
description The c subunit of the ATP synthase is an inner mitochondrial membrane (IMM) protein. Besides its role as the main component of the rotor of the ATP synthase, c subunit from mammalian mitochondria exhibits ion channel activity. In particular, c subunit may be involved in one of the pathways leading to the formation of the permeability transition pore (PTP) during mitochondrial permeability transition (PT), a phenomenon consisting of the permeabilization of the IMM due to high levels of calcium. Our previous study on the synthetic c subunit showed that high concentrations of calcium induce misfolding into cross-β oligomers that form low-conductance channels in model lipid bilayers of about 400 pS. Here, we studied the effect of cyclophilin D (CypD), a mitochondrial chaperone and major regulator of PTP, on the electrophysiological activity of the c subunit to evaluate its role in the functional properties of c subunit. Our study shows that in presence of CypD, c subunit exhibits a larger conductance, up to 4 nS, that could be related to its potential role in mitochondrial toxicity. Further, our results suggest that CypD is necessary for the formation of c subunit induced PTP but may not be an integral part of the pore.
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spelling pubmed-85384902021-10-24 Formation of High-Conductive C Subunit Channels upon Interaction with Cyclophilin D Amodeo, Giuseppe Federico Krilyuk, Natalya Pavlov, Evgeny V. Int J Mol Sci Communication The c subunit of the ATP synthase is an inner mitochondrial membrane (IMM) protein. Besides its role as the main component of the rotor of the ATP synthase, c subunit from mammalian mitochondria exhibits ion channel activity. In particular, c subunit may be involved in one of the pathways leading to the formation of the permeability transition pore (PTP) during mitochondrial permeability transition (PT), a phenomenon consisting of the permeabilization of the IMM due to high levels of calcium. Our previous study on the synthetic c subunit showed that high concentrations of calcium induce misfolding into cross-β oligomers that form low-conductance channels in model lipid bilayers of about 400 pS. Here, we studied the effect of cyclophilin D (CypD), a mitochondrial chaperone and major regulator of PTP, on the electrophysiological activity of the c subunit to evaluate its role in the functional properties of c subunit. Our study shows that in presence of CypD, c subunit exhibits a larger conductance, up to 4 nS, that could be related to its potential role in mitochondrial toxicity. Further, our results suggest that CypD is necessary for the formation of c subunit induced PTP but may not be an integral part of the pore. MDPI 2021-10-13 /pmc/articles/PMC8538490/ /pubmed/34681682 http://dx.doi.org/10.3390/ijms222011022 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Amodeo, Giuseppe Federico
Krilyuk, Natalya
Pavlov, Evgeny V.
Formation of High-Conductive C Subunit Channels upon Interaction with Cyclophilin D
title Formation of High-Conductive C Subunit Channels upon Interaction with Cyclophilin D
title_full Formation of High-Conductive C Subunit Channels upon Interaction with Cyclophilin D
title_fullStr Formation of High-Conductive C Subunit Channels upon Interaction with Cyclophilin D
title_full_unstemmed Formation of High-Conductive C Subunit Channels upon Interaction with Cyclophilin D
title_short Formation of High-Conductive C Subunit Channels upon Interaction with Cyclophilin D
title_sort formation of high-conductive c subunit channels upon interaction with cyclophilin d
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538490/
https://www.ncbi.nlm.nih.gov/pubmed/34681682
http://dx.doi.org/10.3390/ijms222011022
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