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Apoptosis blocks Beclin 1-dependent autophagosome synthesis – an effect rescued by Bcl-xL

Apoptotic cell death is mediated by caspase activation. Autophagy involves the sequestration of cytoplasmic contents into autophagosomes for traffic to lysosomes for degradation. While autophagy is antiapoptotic, increased numbers of autophagosomes have been associated with forms of non-apoptotic ce...

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Detalles Bibliográficos
Autores principales: Luo, S, Rubinsztein, D C.
Formato: Texto
Lenguaje:English
Publicado: 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894406/
https://www.ncbi.nlm.nih.gov/pubmed/19713971
http://dx.doi.org/10.1038/cdd.2009.121
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author Luo, S
Rubinsztein, D C.
author_facet Luo, S
Rubinsztein, D C.
author_sort Luo, S
collection PubMed
description Apoptotic cell death is mediated by caspase activation. Autophagy involves the sequestration of cytoplasmic contents into autophagosomes for traffic to lysosomes for degradation. While autophagy is antiapoptotic, increased numbers of autophagosomes have been associated with forms of non-apoptotic cell death. Apoptosis and autophagy may be co-regulated in the same directions, as the anti-apoptotic Bcl-2 and Bcl-xL proteins negatively regulate autophagy by binding to Beclin 1 (mammalian Atg6), and pro-apoptotic BH3-only proteins may reverse this effect by displacing these interactions. Here we show that apoptosis can suppress autophagy. Apoptosis induced by the pro-apoptotic protein Bax reduced autophagy by enhancing caspase-mediated cleavage of Beclin 1 at D149. After cleavage, both N and C-terminal Beclin 1 fragments change their localisations and these fragments do not interact normally with Vps34, which is required for autophagy. The cleavage of Beclin 1 is a critical event whereby caspases inhibit autophagy, as a non-cleavable Beclin 1 mutant restored autophagy in cells overexpressing Bax.
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spelling pubmed-28944062010-08-01 Apoptosis blocks Beclin 1-dependent autophagosome synthesis – an effect rescued by Bcl-xL Luo, S Rubinsztein, D C. Cell Death Differ Article Apoptotic cell death is mediated by caspase activation. Autophagy involves the sequestration of cytoplasmic contents into autophagosomes for traffic to lysosomes for degradation. While autophagy is antiapoptotic, increased numbers of autophagosomes have been associated with forms of non-apoptotic cell death. Apoptosis and autophagy may be co-regulated in the same directions, as the anti-apoptotic Bcl-2 and Bcl-xL proteins negatively regulate autophagy by binding to Beclin 1 (mammalian Atg6), and pro-apoptotic BH3-only proteins may reverse this effect by displacing these interactions. Here we show that apoptosis can suppress autophagy. Apoptosis induced by the pro-apoptotic protein Bax reduced autophagy by enhancing caspase-mediated cleavage of Beclin 1 at D149. After cleavage, both N and C-terminal Beclin 1 fragments change their localisations and these fragments do not interact normally with Vps34, which is required for autophagy. The cleavage of Beclin 1 is a critical event whereby caspases inhibit autophagy, as a non-cleavable Beclin 1 mutant restored autophagy in cells overexpressing Bax. 2009-08-28 2010-02 /pmc/articles/PMC2894406/ /pubmed/19713971 http://dx.doi.org/10.1038/cdd.2009.121 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Luo, S
Rubinsztein, D C.
Apoptosis blocks Beclin 1-dependent autophagosome synthesis – an effect rescued by Bcl-xL
title Apoptosis blocks Beclin 1-dependent autophagosome synthesis – an effect rescued by Bcl-xL
title_full Apoptosis blocks Beclin 1-dependent autophagosome synthesis – an effect rescued by Bcl-xL
title_fullStr Apoptosis blocks Beclin 1-dependent autophagosome synthesis – an effect rescued by Bcl-xL
title_full_unstemmed Apoptosis blocks Beclin 1-dependent autophagosome synthesis – an effect rescued by Bcl-xL
title_short Apoptosis blocks Beclin 1-dependent autophagosome synthesis – an effect rescued by Bcl-xL
title_sort apoptosis blocks beclin 1-dependent autophagosome synthesis – an effect rescued by bcl-xl
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894406/
https://www.ncbi.nlm.nih.gov/pubmed/19713971
http://dx.doi.org/10.1038/cdd.2009.121
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