Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy.
EMBO J
; 30(7): 1195-208, 2011 Apr 06.
Article
em En
| MEDLINE
| ID: mdl-21358617
ABSTRACT
BECLIN 1 is a central player in macroautophagy. AMBRA1, a BECLIN 1-interacting protein, positively regulates the BECLIN 1-dependent programme of autophagy. In this study, we show that AMBRA1 binds preferentially the mitochondrial pool of the antiapoptotic factor BCL-2, and that this interaction is disrupted following autophagy induction. Further, AMBRA1 can compete with both mitochondrial and endoplasmic reticulum-resident BCL-2 (mito-BCL-2 and ER-BCL-2, respectively) to bind BECLIN 1. Moreover, after autophagy induction, AMBRA1 is recruited to BECLIN 1. Altogether, these results indicate that, in normal conditions, a pool of AMBRA1 binds preferentially mito-BCL-2; after autophagy induction, AMBRA1 is released from BCL-2, consistent with its ability to promote BECLIN 1 activity. In addition, we found that the binding between AMBRA1 and mito-BCL-2 is reduced during apoptosis. Thus, a dynamic interaction exists between AMBRA1 and BCL-2 at the mitochondria that could regulate both BECLIN 1-dependent autophagy and apoptosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Proteínas de Transporte
/
Regulação da Expressão Gênica
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Proteínas Proto-Oncogênicas c-bcl-2
/
Mapeamento de Interação de Proteínas
Limite:
Humans
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Itália