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.

Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy / Strappazzon, Flavie; Vietri-Rudan, Matteo; Campello, Silvia; Nazio, Francesca; Florenzano, Fulvio; Fimia, Gian Maria; Piacentini, Mauro; Levine, Beth; Cecconi, Francesco. - In: EMBO JOURNAL. - ISSN 1460-2075. - 30:7(2011), pp. 1195-1208. [10.1038/emboj.2011.49]

Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy

Fimia Gian Maria;
2011

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.
2011
Adaptor Proteins; Signal Transducing; Apoptosis Regulatory Proteins; Carrier Proteins; Cell Line; Endoplasmic Reticulum; Humans; Membrane Proteins; Mitochondrial Membranes; Proto-Oncogene Proteins c-bcl-2; Autophagy; Gene Expression Regulation; Protein Interaction Mapping
01 Pubblicazione su rivista::01a Articolo in rivista
Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy / Strappazzon, Flavie; Vietri-Rudan, Matteo; Campello, Silvia; Nazio, Francesca; Florenzano, Fulvio; Fimia, Gian Maria; Piacentini, Mauro; Levine, Beth; Cecconi, Francesco. - In: EMBO JOURNAL. - ISSN 1460-2075. - 30:7(2011), pp. 1195-1208. [10.1038/emboj.2011.49]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1319234
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 197
  • ???jsp.display-item.citation.isi??? 181
social impact