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.

Strappazzon, F., Vietri Rudan, M., Campello, S., Nazio, F., Florenzano, F., Fimia, G., et al. (2011). Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy. EMBO JOURNAL, 30(7), 1195-1208 [10.1038/emboj.2011.49].

Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy

CAMPELLO, SILVIA;Nazio, F;PIACENTINI, MAURO;CECCONI, FRANCESCO
2011-04-06

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.
6-apr-2011
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/06 - ANATOMIA COMPARATA E CITOLOGIA
English
Con Impact Factor ISI
Cell Line; Endoplasmic Reticulum; Mitochondrial Membranes; Proto-Oncogene Proteins c-bcl-2; Autophagy; Protein Interaction Mapping; Membrane Proteins; Gene Expression Regulation; Carrier Proteins; Apoptosis Regulatory Proteins; Humans
Strappazzon, F., Vietri Rudan, M., Campello, S., Nazio, F., Florenzano, F., Fimia, G., et al. (2011). Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy. EMBO JOURNAL, 30(7), 1195-1208 [10.1038/emboj.2011.49].
Strappazzon, F; Vietri Rudan, M; Campello, S; Nazio, F; Florenzano, F; Fimia, G; Piacentini, M; Levine, B; Cecconi, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/18323
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