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.

Autore Pugliese

• Fimia Gian Maria

Tutti gli autori

• Strappazzon F. , Vietri-Rudan M. , Campello S. , Nazio F. , Florenzano F. , Fimia G.M. , Piacentini M. , Levine B. , Cecconi F.

Titolo volume/Rivista

EMBO JOURNAL

Anno di pubblicazione

2011

ISSN

1460-2075

ISBN

Non Disponibile

Numero di citazioni Wos

98

Ultimo Aggiornamento Citazioni

28/04/2018

Numero di citazioni Scopus

101

Ultimo Aggiornamento Citazioni

28/04/2018

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile