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Bcl-x(L) regulates mitochondrial energetics by stabilizing the inner membrane potential
Mammalian Bcl-x(L) protein localizes to the outer mitochondrial membrane, where it inhibits apoptosis by binding Bax and inhibiting Bax-induced outer membrane permeabilization. Contrary to expectation, we found by electron microscopy and biochemical approaches that endogenous Bcl-x(L) also localized...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198165/ https://www.ncbi.nlm.nih.gov/pubmed/21987637 http://dx.doi.org/10.1083/jcb.201108059 |
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author | Chen, Ying-bei Aon, Miguel A. Hsu, Yi-Te Soane, Lucian Teng, Xinchen McCaffery, J. Michael Cheng, Wen-Chih Qi, Bing Li, Hongmei Alavian, Kambiz N. Dayhoff-Brannigan, Margaret Zou, Shifa Pineda, Fernando J. O'Rourke, Brian Ko, Young H. Pedersen, Peter L. Kaczmarek, Leonard K. Jonas, Elizabeth A. Hardwick, J. Marie |
author_facet | Chen, Ying-bei Aon, Miguel A. Hsu, Yi-Te Soane, Lucian Teng, Xinchen McCaffery, J. Michael Cheng, Wen-Chih Qi, Bing Li, Hongmei Alavian, Kambiz N. Dayhoff-Brannigan, Margaret Zou, Shifa Pineda, Fernando J. O'Rourke, Brian Ko, Young H. Pedersen, Peter L. Kaczmarek, Leonard K. Jonas, Elizabeth A. Hardwick, J. Marie |
author_sort | Chen, Ying-bei |
collection | PubMed |
description | Mammalian Bcl-x(L) protein localizes to the outer mitochondrial membrane, where it inhibits apoptosis by binding Bax and inhibiting Bax-induced outer membrane permeabilization. Contrary to expectation, we found by electron microscopy and biochemical approaches that endogenous Bcl-x(L) also localized to inner mitochondrial cristae. Two-photon microscopy of cultured neurons revealed large fluctuations in inner mitochondrial membrane potential when Bcl-x(L) was genetically deleted or pharmacologically inhibited, indicating increased total ion flux into and out of mitochondria. Computational, biochemical, and genetic evidence indicated that Bcl-x(L) reduces futile ion flux across the inner mitochondrial membrane to prevent a wasteful drain on cellular resources, thereby preventing an energetic crisis during stress. Given that F(1)F(O)–ATP synthase directly affects mitochondrial membrane potential and having identified the mitochondrial ATP synthase β subunit in a screen for Bcl-x(L)–binding partners, we tested and found that Bcl-x(L) failed to protect β subunit–deficient yeast. Thus, by bolstering mitochondrial energetic capacity, Bcl-x(L) may contribute importantly to cell survival independently of other Bcl-2 family proteins. |
format | Online Article Text |
id | pubmed-3198165 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-31981652012-04-17 Bcl-x(L) regulates mitochondrial energetics by stabilizing the inner membrane potential Chen, Ying-bei Aon, Miguel A. Hsu, Yi-Te Soane, Lucian Teng, Xinchen McCaffery, J. Michael Cheng, Wen-Chih Qi, Bing Li, Hongmei Alavian, Kambiz N. Dayhoff-Brannigan, Margaret Zou, Shifa Pineda, Fernando J. O'Rourke, Brian Ko, Young H. Pedersen, Peter L. Kaczmarek, Leonard K. Jonas, Elizabeth A. Hardwick, J. Marie J Cell Biol Research Articles Mammalian Bcl-x(L) protein localizes to the outer mitochondrial membrane, where it inhibits apoptosis by binding Bax and inhibiting Bax-induced outer membrane permeabilization. Contrary to expectation, we found by electron microscopy and biochemical approaches that endogenous Bcl-x(L) also localized to inner mitochondrial cristae. Two-photon microscopy of cultured neurons revealed large fluctuations in inner mitochondrial membrane potential when Bcl-x(L) was genetically deleted or pharmacologically inhibited, indicating increased total ion flux into and out of mitochondria. Computational, biochemical, and genetic evidence indicated that Bcl-x(L) reduces futile ion flux across the inner mitochondrial membrane to prevent a wasteful drain on cellular resources, thereby preventing an energetic crisis during stress. Given that F(1)F(O)–ATP synthase directly affects mitochondrial membrane potential and having identified the mitochondrial ATP synthase β subunit in a screen for Bcl-x(L)–binding partners, we tested and found that Bcl-x(L) failed to protect β subunit–deficient yeast. Thus, by bolstering mitochondrial energetic capacity, Bcl-x(L) may contribute importantly to cell survival independently of other Bcl-2 family proteins. The Rockefeller University Press 2011-10-17 /pmc/articles/PMC3198165/ /pubmed/21987637 http://dx.doi.org/10.1083/jcb.201108059 Text en © 2011 Chen et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Chen, Ying-bei Aon, Miguel A. Hsu, Yi-Te Soane, Lucian Teng, Xinchen McCaffery, J. Michael Cheng, Wen-Chih Qi, Bing Li, Hongmei Alavian, Kambiz N. Dayhoff-Brannigan, Margaret Zou, Shifa Pineda, Fernando J. O'Rourke, Brian Ko, Young H. Pedersen, Peter L. Kaczmarek, Leonard K. Jonas, Elizabeth A. Hardwick, J. Marie Bcl-x(L) regulates mitochondrial energetics by stabilizing the inner membrane potential |
title | Bcl-x(L) regulates mitochondrial energetics by stabilizing
the inner membrane potential |
title_full | Bcl-x(L) regulates mitochondrial energetics by stabilizing
the inner membrane potential |
title_fullStr | Bcl-x(L) regulates mitochondrial energetics by stabilizing
the inner membrane potential |
title_full_unstemmed | Bcl-x(L) regulates mitochondrial energetics by stabilizing
the inner membrane potential |
title_short | Bcl-x(L) regulates mitochondrial energetics by stabilizing
the inner membrane potential |
title_sort | bcl-x(l) regulates mitochondrial energetics by stabilizing
the inner membrane potential |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198165/ https://www.ncbi.nlm.nih.gov/pubmed/21987637 http://dx.doi.org/10.1083/jcb.201108059 |
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