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Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions

The mitochondrial permeability transition (mPT) describes a Ca(2+)-dependent and cyclophilin D (CypD)-facilitated increase of inner mitochondrial membrane permeability that allows diffusion of molecules up to 1.5 kDa in size. It is mediated by a non-selective channel, the mitochondrial permeability...

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Autores principales: Bernardi, Paolo, Gerle, Christoph, Halestrap, Andrew P., Jonas, Elizabeth A., Karch, Jason, Mnatsakanyan, Nelli, Pavlov, Evgeny, Sheu, Shey-Shing, Soukas, Alexander A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406888/
https://www.ncbi.nlm.nih.gov/pubmed/37460667
http://dx.doi.org/10.1038/s41418-023-01187-0
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author Bernardi, Paolo
Gerle, Christoph
Halestrap, Andrew P.
Jonas, Elizabeth A.
Karch, Jason
Mnatsakanyan, Nelli
Pavlov, Evgeny
Sheu, Shey-Shing
Soukas, Alexander A.
author_facet Bernardi, Paolo
Gerle, Christoph
Halestrap, Andrew P.
Jonas, Elizabeth A.
Karch, Jason
Mnatsakanyan, Nelli
Pavlov, Evgeny
Sheu, Shey-Shing
Soukas, Alexander A.
author_sort Bernardi, Paolo
collection PubMed
description The mitochondrial permeability transition (mPT) describes a Ca(2+)-dependent and cyclophilin D (CypD)-facilitated increase of inner mitochondrial membrane permeability that allows diffusion of molecules up to 1.5 kDa in size. It is mediated by a non-selective channel, the mitochondrial permeability transition pore (mPTP). Sustained mPTP opening causes mitochondrial swelling, which ruptures the outer mitochondrial membrane leading to subsequent apoptotic and necrotic cell death, and is implicated in a range of pathologies. However, transient mPTP opening at various sub-conductance states may contribute several physiological roles such as alterations in mitochondrial bioenergetics and rapid Ca(2+) efflux. Since its discovery decades ago, intensive efforts have been made to identify the exact pore-forming structure of the mPT. Both the adenine nucleotide translocase (ANT) and, more recently, the mitochondrial F(1)F(O) (F)-ATP synthase dimers, monomers or c-subunit ring alone have been implicated. Here we share the insights of several key investigators with different perspectives who have pioneered mPT research. We critically assess proposed models for the molecular identity of the mPTP and the mechanisms underlying its opposing roles in the life and death of cells. We provide in-depth insights into current controversies, seeking to achieve a degree of consensus that will stimulate future innovative research into the nature and role of the mPTP.
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spelling pubmed-104068882023-08-09 Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions Bernardi, Paolo Gerle, Christoph Halestrap, Andrew P. Jonas, Elizabeth A. Karch, Jason Mnatsakanyan, Nelli Pavlov, Evgeny Sheu, Shey-Shing Soukas, Alexander A. Cell Death Differ Review Article The mitochondrial permeability transition (mPT) describes a Ca(2+)-dependent and cyclophilin D (CypD)-facilitated increase of inner mitochondrial membrane permeability that allows diffusion of molecules up to 1.5 kDa in size. It is mediated by a non-selective channel, the mitochondrial permeability transition pore (mPTP). Sustained mPTP opening causes mitochondrial swelling, which ruptures the outer mitochondrial membrane leading to subsequent apoptotic and necrotic cell death, and is implicated in a range of pathologies. However, transient mPTP opening at various sub-conductance states may contribute several physiological roles such as alterations in mitochondrial bioenergetics and rapid Ca(2+) efflux. Since its discovery decades ago, intensive efforts have been made to identify the exact pore-forming structure of the mPT. Both the adenine nucleotide translocase (ANT) and, more recently, the mitochondrial F(1)F(O) (F)-ATP synthase dimers, monomers or c-subunit ring alone have been implicated. Here we share the insights of several key investigators with different perspectives who have pioneered mPT research. We critically assess proposed models for the molecular identity of the mPTP and the mechanisms underlying its opposing roles in the life and death of cells. We provide in-depth insights into current controversies, seeking to achieve a degree of consensus that will stimulate future innovative research into the nature and role of the mPTP. Nature Publishing Group UK 2023-07-17 2023-08 /pmc/articles/PMC10406888/ /pubmed/37460667 http://dx.doi.org/10.1038/s41418-023-01187-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Review Article
Bernardi, Paolo
Gerle, Christoph
Halestrap, Andrew P.
Jonas, Elizabeth A.
Karch, Jason
Mnatsakanyan, Nelli
Pavlov, Evgeny
Sheu, Shey-Shing
Soukas, Alexander A.
Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions
title Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions
title_full Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions
title_fullStr Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions
title_full_unstemmed Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions
title_short Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions
title_sort identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406888/
https://www.ncbi.nlm.nih.gov/pubmed/37460667
http://dx.doi.org/10.1038/s41418-023-01187-0
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