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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8538490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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