Bax translocation to mitochondria subsequent to a rapid loss of mitochondrial membrane potential
Autor(a) principal: | |
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Data de Publicação: | 2001 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://dx.doi.org/10.1038/sj.cdd.4400889 http://repositorio.unifesp.br/handle/11600/26609 |
Resumo: | Bax, a pro-apoptotic member of the Bcl-2 family, is a cytosolic protein that inserts into mitochondrial membranes upon induction of cell death. Using the green fluorescent protein fused to Bax (GFP-Bax) to quantitate mitochondrial binding in living cells we have investigated the cause of Bax association with mitochondria and the time course relative to endogenous and induced changes in mitochondrial membrane potential (Delta Psi (m)). We have found that staurosporine (STS) induces a loss in Delta Psi (m) before GFP-Bax translocation can be measured. the onset of the Delta Psi (m) loss is followed by a rapid and complete collapse of Delta Psi (m) which is followed by Bax association with mitochondria. the mitochondria uncoupler FCCP, in the presence of the F-1-F-0 ATPase inhibitor oligomycin, can trigger Bax translocation to mitochondria suggesting that when ATP levels are maintained a collapse of Delta Psi (m) induces Bax translocation. Neither FCCP nor oligomycin alone alters Bax location. Bax association with mitochondria is also triggered by inhibitors of the electron transport chain, antimycin and rotenone, compounds that collapse Delta Psi (m) without inducing rapid ATP hydrolysis that typically occurs with uncouplers such as FCCP. Taken together, our results suggest that alterations in mitochondrial energization associated with apoptosis can initiate Bax docking to mitochondria. |
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Bax translocation to mitochondria subsequent to a rapid loss of mitochondrial membrane potentialmitochondriaBaxmitochondrial membrane potentialmitochondrial inhibitorsBax, a pro-apoptotic member of the Bcl-2 family, is a cytosolic protein that inserts into mitochondrial membranes upon induction of cell death. Using the green fluorescent protein fused to Bax (GFP-Bax) to quantitate mitochondrial binding in living cells we have investigated the cause of Bax association with mitochondria and the time course relative to endogenous and induced changes in mitochondrial membrane potential (Delta Psi (m)). We have found that staurosporine (STS) induces a loss in Delta Psi (m) before GFP-Bax translocation can be measured. the onset of the Delta Psi (m) loss is followed by a rapid and complete collapse of Delta Psi (m) which is followed by Bax association with mitochondria. the mitochondria uncoupler FCCP, in the presence of the F-1-F-0 ATPase inhibitor oligomycin, can trigger Bax translocation to mitochondria suggesting that when ATP levels are maintained a collapse of Delta Psi (m) induces Bax translocation. Neither FCCP nor oligomycin alone alters Bax location. Bax association with mitochondria is also triggered by inhibitors of the electron transport chain, antimycin and rotenone, compounds that collapse Delta Psi (m) without inducing rapid ATP hydrolysis that typically occurs with uncouplers such as FCCP. Taken together, our results suggest that alterations in mitochondrial energization associated with apoptosis can initiate Bax docking to mitochondria.NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USAUniversidade Federal de São Paulo, Dept Farmacol, São Paulo, BrazilNICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USAMed Univ S Carolina, Charleston, SC 29425 USAUniversidade Federal de São Paulo, Dept Farmacol, São Paulo, BrazilWeb of ScienceNature Publishing GroupNINDSUniversidade Federal de São Paulo (UNIFESP)NICHHDMed Univ S CarolinaSmaili, Soraya Soubhi [UNIFESP]Hsu, Y. T.Sanders, K. M.Russel, J. T.Youle, R. J.2016-01-24T12:31:27Z2016-01-24T12:31:27Z2001-09-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion909-920http://dx.doi.org/10.1038/sj.cdd.4400889Cell Death and Differentiation. Basingstoke: Nature Publishing Group, v. 8, n. 9, p. 909-920, 2001.10.1038/sj.cdd.44008891350-9047http://repositorio.unifesp.br/handle/11600/26609WOS:000170472300005engCell Death and Differentiationinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2023-05-18T13:50:59Zoai:repositorio.unifesp.br/:11600/26609Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652023-05-18T13:50:59Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.none.fl_str_mv |
Bax translocation to mitochondria subsequent to a rapid loss of mitochondrial membrane potential |
title |
Bax translocation to mitochondria subsequent to a rapid loss of mitochondrial membrane potential |
spellingShingle |
Bax translocation to mitochondria subsequent to a rapid loss of mitochondrial membrane potential Smaili, Soraya Soubhi [UNIFESP] mitochondria Bax mitochondrial membrane potential mitochondrial inhibitors |
title_short |
Bax translocation to mitochondria subsequent to a rapid loss of mitochondrial membrane potential |
title_full |
Bax translocation to mitochondria subsequent to a rapid loss of mitochondrial membrane potential |
title_fullStr |
Bax translocation to mitochondria subsequent to a rapid loss of mitochondrial membrane potential |
title_full_unstemmed |
Bax translocation to mitochondria subsequent to a rapid loss of mitochondrial membrane potential |
title_sort |
Bax translocation to mitochondria subsequent to a rapid loss of mitochondrial membrane potential |
author |
Smaili, Soraya Soubhi [UNIFESP] |
author_facet |
Smaili, Soraya Soubhi [UNIFESP] Hsu, Y. T. Sanders, K. M. Russel, J. T. Youle, R. J. |
author_role |
author |
author2 |
Hsu, Y. T. Sanders, K. M. Russel, J. T. Youle, R. J. |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
NINDS Universidade Federal de São Paulo (UNIFESP) NICHHD Med Univ S Carolina |
dc.contributor.author.fl_str_mv |
Smaili, Soraya Soubhi [UNIFESP] Hsu, Y. T. Sanders, K. M. Russel, J. T. Youle, R. J. |
dc.subject.por.fl_str_mv |
mitochondria Bax mitochondrial membrane potential mitochondrial inhibitors |
topic |
mitochondria Bax mitochondrial membrane potential mitochondrial inhibitors |
description |
Bax, a pro-apoptotic member of the Bcl-2 family, is a cytosolic protein that inserts into mitochondrial membranes upon induction of cell death. Using the green fluorescent protein fused to Bax (GFP-Bax) to quantitate mitochondrial binding in living cells we have investigated the cause of Bax association with mitochondria and the time course relative to endogenous and induced changes in mitochondrial membrane potential (Delta Psi (m)). We have found that staurosporine (STS) induces a loss in Delta Psi (m) before GFP-Bax translocation can be measured. the onset of the Delta Psi (m) loss is followed by a rapid and complete collapse of Delta Psi (m) which is followed by Bax association with mitochondria. the mitochondria uncoupler FCCP, in the presence of the F-1-F-0 ATPase inhibitor oligomycin, can trigger Bax translocation to mitochondria suggesting that when ATP levels are maintained a collapse of Delta Psi (m) induces Bax translocation. Neither FCCP nor oligomycin alone alters Bax location. Bax association with mitochondria is also triggered by inhibitors of the electron transport chain, antimycin and rotenone, compounds that collapse Delta Psi (m) without inducing rapid ATP hydrolysis that typically occurs with uncouplers such as FCCP. Taken together, our results suggest that alterations in mitochondrial energization associated with apoptosis can initiate Bax docking to mitochondria. |
publishDate |
2001 |
dc.date.none.fl_str_mv |
2001-09-01 2016-01-24T12:31:27Z 2016-01-24T12:31:27Z |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1038/sj.cdd.4400889 Cell Death and Differentiation. Basingstoke: Nature Publishing Group, v. 8, n. 9, p. 909-920, 2001. 10.1038/sj.cdd.4400889 1350-9047 http://repositorio.unifesp.br/handle/11600/26609 WOS:000170472300005 |
url |
http://dx.doi.org/10.1038/sj.cdd.4400889 http://repositorio.unifesp.br/handle/11600/26609 |
identifier_str_mv |
Cell Death and Differentiation. Basingstoke: Nature Publishing Group, v. 8, n. 9, p. 909-920, 2001. 10.1038/sj.cdd.4400889 1350-9047 WOS:000170472300005 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Cell Death and Differentiation |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
909-920 |
dc.publisher.none.fl_str_mv |
Nature Publishing Group |
publisher.none.fl_str_mv |
Nature Publishing Group |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
biblioteca.csp@unifesp.br |
_version_ |
1814268343063937024 |