Cargando…
AMP kinase–mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis
Excitotoxicity after glutamate receptor overactivation induces disturbances in cellular ion gradients, resulting in necrosis or apoptosis. Excitotoxic necrosis is triggered by rapid, irreversible ATP depletion, whereas the ability to recover cellular bioenergetics is suggested to be necessary for th...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2010
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854380/ https://www.ncbi.nlm.nih.gov/pubmed/20351066 http://dx.doi.org/10.1083/jcb.200909166 |
_version_ | 1782180095241224192 |
---|---|
author | Concannon, Caoimhín G. Tuffy, Liam P. Weisová, Petronela Bonner, Helena P. Dávila, David Bonner, Caroline Devocelle, Marc C. Strasser, Andreas Ward, Manus W. Prehn, Jochen H.M. |
author_facet | Concannon, Caoimhín G. Tuffy, Liam P. Weisová, Petronela Bonner, Helena P. Dávila, David Bonner, Caroline Devocelle, Marc C. Strasser, Andreas Ward, Manus W. Prehn, Jochen H.M. |
author_sort | Concannon, Caoimhín G. |
collection | PubMed |
description | Excitotoxicity after glutamate receptor overactivation induces disturbances in cellular ion gradients, resulting in necrosis or apoptosis. Excitotoxic necrosis is triggered by rapid, irreversible ATP depletion, whereas the ability to recover cellular bioenergetics is suggested to be necessary for the activation of excitotoxic apoptosis. In this study, we demonstrate that even a transient decrease in cellular bioenergetics and an associated activation of adenosine monophosphate–activated protein kinase (AMPK) is necessary for the activation of excitotoxic apoptosis. We show that the Bcl-2 homology domain 3 (BH3)–only protein Bim, a proapoptotic Bcl-2 family member, is activated in multiple excitotoxicity paradigms, mediates excitotoxic apoptosis, and inhibits delayed Ca(2+) deregulation, mitochondrial depolarization, and apoptosis-inducing factor translocation. We demonstrate that bim activation required the activation of AMPK and that prolonged AMPK activation is sufficient to induce bim gene expression and to trigger a bim-dependent cell death. Collectively, our data demonstrate that AMPK activation and the BH3-only protein Bim couple transient energy depletion to stress-induced neuronal apoptosis. |
format | Text |
id | pubmed-2854380 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28543802010-10-05 AMP kinase–mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis Concannon, Caoimhín G. Tuffy, Liam P. Weisová, Petronela Bonner, Helena P. Dávila, David Bonner, Caroline Devocelle, Marc C. Strasser, Andreas Ward, Manus W. Prehn, Jochen H.M. J Cell Biol Research Articles Excitotoxicity after glutamate receptor overactivation induces disturbances in cellular ion gradients, resulting in necrosis or apoptosis. Excitotoxic necrosis is triggered by rapid, irreversible ATP depletion, whereas the ability to recover cellular bioenergetics is suggested to be necessary for the activation of excitotoxic apoptosis. In this study, we demonstrate that even a transient decrease in cellular bioenergetics and an associated activation of adenosine monophosphate–activated protein kinase (AMPK) is necessary for the activation of excitotoxic apoptosis. We show that the Bcl-2 homology domain 3 (BH3)–only protein Bim, a proapoptotic Bcl-2 family member, is activated in multiple excitotoxicity paradigms, mediates excitotoxic apoptosis, and inhibits delayed Ca(2+) deregulation, mitochondrial depolarization, and apoptosis-inducing factor translocation. We demonstrate that bim activation required the activation of AMPK and that prolonged AMPK activation is sufficient to induce bim gene expression and to trigger a bim-dependent cell death. Collectively, our data demonstrate that AMPK activation and the BH3-only protein Bim couple transient energy depletion to stress-induced neuronal apoptosis. The Rockefeller University Press 2010-04-05 /pmc/articles/PMC2854380/ /pubmed/20351066 http://dx.doi.org/10.1083/jcb.200909166 Text en © 2010 Concannon 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 Concannon, Caoimhín G. Tuffy, Liam P. Weisová, Petronela Bonner, Helena P. Dávila, David Bonner, Caroline Devocelle, Marc C. Strasser, Andreas Ward, Manus W. Prehn, Jochen H.M. AMP kinase–mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis |
title | AMP kinase–mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis |
title_full | AMP kinase–mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis |
title_fullStr | AMP kinase–mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis |
title_full_unstemmed | AMP kinase–mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis |
title_short | AMP kinase–mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis |
title_sort | amp kinase–mediated activation of the bh3-only protein bim couples energy depletion to stress-induced apoptosis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854380/ https://www.ncbi.nlm.nih.gov/pubmed/20351066 http://dx.doi.org/10.1083/jcb.200909166 |
work_keys_str_mv | AT concannoncaoimhing ampkinasemediatedactivationofthebh3onlyproteinbimcouplesenergydepletiontostressinducedapoptosis AT tuffyliamp ampkinasemediatedactivationofthebh3onlyproteinbimcouplesenergydepletiontostressinducedapoptosis AT weisovapetronela ampkinasemediatedactivationofthebh3onlyproteinbimcouplesenergydepletiontostressinducedapoptosis AT bonnerhelenap ampkinasemediatedactivationofthebh3onlyproteinbimcouplesenergydepletiontostressinducedapoptosis AT daviladavid ampkinasemediatedactivationofthebh3onlyproteinbimcouplesenergydepletiontostressinducedapoptosis AT bonnercaroline ampkinasemediatedactivationofthebh3onlyproteinbimcouplesenergydepletiontostressinducedapoptosis AT devocellemarcc ampkinasemediatedactivationofthebh3onlyproteinbimcouplesenergydepletiontostressinducedapoptosis AT strasserandreas ampkinasemediatedactivationofthebh3onlyproteinbimcouplesenergydepletiontostressinducedapoptosis AT wardmanusw ampkinasemediatedactivationofthebh3onlyproteinbimcouplesenergydepletiontostressinducedapoptosis AT prehnjochenhm ampkinasemediatedactivationofthebh3onlyproteinbimcouplesenergydepletiontostressinducedapoptosis |