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Bax-induced Cytochrome C Release from Mitochondria Is Independent of the Permeability Transition Pore but Highly Dependent on Mg(2+) Ions

Bcl-2 family members either promote or repress programmed cell death. Bax, a death-promoting member, is a pore-forming, mitochondria-associated protein whose mechanism of action is still unknown. During apoptosis, cytochrome C is released from the mitochondria into the cytosol where it binds to APAF...

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Autores principales: Eskes, Robert, Antonsson, Bruno, Osen-Sand, Astrid, Montessuit, Sylvie, Richter, Christoph, Sadoul, Rémy, Mazzei, Gonzalo, Nichols, Anthony, Martinou, Jean-Claude
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1998
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2132823/
https://www.ncbi.nlm.nih.gov/pubmed/9763433
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author Eskes, Robert
Antonsson, Bruno
Osen-Sand, Astrid
Montessuit, Sylvie
Richter, Christoph
Sadoul, Rémy
Mazzei, Gonzalo
Nichols, Anthony
Martinou, Jean-Claude
author_facet Eskes, Robert
Antonsson, Bruno
Osen-Sand, Astrid
Montessuit, Sylvie
Richter, Christoph
Sadoul, Rémy
Mazzei, Gonzalo
Nichols, Anthony
Martinou, Jean-Claude
author_sort Eskes, Robert
collection PubMed
description Bcl-2 family members either promote or repress programmed cell death. Bax, a death-promoting member, is a pore-forming, mitochondria-associated protein whose mechanism of action is still unknown. During apoptosis, cytochrome C is released from the mitochondria into the cytosol where it binds to APAF-1, a mammalian homologue of Ced-4, and participates in the activation of caspases. The release of cytochrome C has been postulated to be a consequence of the opening of the mitochondrial permeability transition pore (PTP). We now report that Bax is sufficient to trigger the release of cytochrome C from isolated mitochondria. This pathway is distinct from the previously described calcium-inducible, cyclosporin A–sensitive PTP. Rather, the cytochrome C release induced by Bax is facilitated by Mg(2+) and cannot be blocked by PTP inhibitors. These results strongly suggest the existence of two distinct mechanisms leading to cytochrome C release: one stimulated by calcium and inhibited by cyclosporin A, the other Bax dependent, Mg(2+) sensitive but cyclosporin insensitive.
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spelling pubmed-21328232008-05-01 Bax-induced Cytochrome C Release from Mitochondria Is Independent of the Permeability Transition Pore but Highly Dependent on Mg(2+) Ions Eskes, Robert Antonsson, Bruno Osen-Sand, Astrid Montessuit, Sylvie Richter, Christoph Sadoul, Rémy Mazzei, Gonzalo Nichols, Anthony Martinou, Jean-Claude J Cell Biol Regular Articles Bcl-2 family members either promote or repress programmed cell death. Bax, a death-promoting member, is a pore-forming, mitochondria-associated protein whose mechanism of action is still unknown. During apoptosis, cytochrome C is released from the mitochondria into the cytosol where it binds to APAF-1, a mammalian homologue of Ced-4, and participates in the activation of caspases. The release of cytochrome C has been postulated to be a consequence of the opening of the mitochondrial permeability transition pore (PTP). We now report that Bax is sufficient to trigger the release of cytochrome C from isolated mitochondria. This pathway is distinct from the previously described calcium-inducible, cyclosporin A–sensitive PTP. Rather, the cytochrome C release induced by Bax is facilitated by Mg(2+) and cannot be blocked by PTP inhibitors. These results strongly suggest the existence of two distinct mechanisms leading to cytochrome C release: one stimulated by calcium and inhibited by cyclosporin A, the other Bax dependent, Mg(2+) sensitive but cyclosporin insensitive. The Rockefeller University Press 1998-10-05 /pmc/articles/PMC2132823/ /pubmed/9763433 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Regular Articles
Eskes, Robert
Antonsson, Bruno
Osen-Sand, Astrid
Montessuit, Sylvie
Richter, Christoph
Sadoul, Rémy
Mazzei, Gonzalo
Nichols, Anthony
Martinou, Jean-Claude
Bax-induced Cytochrome C Release from Mitochondria Is Independent of the Permeability Transition Pore but Highly Dependent on Mg(2+) Ions
title Bax-induced Cytochrome C Release from Mitochondria Is Independent of the Permeability Transition Pore but Highly Dependent on Mg(2+) Ions
title_full Bax-induced Cytochrome C Release from Mitochondria Is Independent of the Permeability Transition Pore but Highly Dependent on Mg(2+) Ions
title_fullStr Bax-induced Cytochrome C Release from Mitochondria Is Independent of the Permeability Transition Pore but Highly Dependent on Mg(2+) Ions
title_full_unstemmed Bax-induced Cytochrome C Release from Mitochondria Is Independent of the Permeability Transition Pore but Highly Dependent on Mg(2+) Ions
title_short Bax-induced Cytochrome C Release from Mitochondria Is Independent of the Permeability Transition Pore but Highly Dependent on Mg(2+) Ions
title_sort bax-induced cytochrome c release from mitochondria is independent of the permeability transition pore but highly dependent on mg(2+) ions
topic Regular Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2132823/
https://www.ncbi.nlm.nih.gov/pubmed/9763433
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