Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy

Flavie Strappazzon, Matteo Vietri-Rudan, Silvia Campello, Francesca Nazio, Fulvio Florenzano, Gian Maria Fimia, Mauro Piacentini, Beth Levine, Francesco Cecconi

Research output: Contribution to journalArticle

139 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1195-1208
Number of pages14
JournalEMBO Journal
Volume30
Issue number7
DOIs
StatePublished - Apr 6 2011

Keywords

  • apoptosis
  • autophagy
  • endoplasmic reticulum
  • mitochondria

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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  • Cite this

    Strappazzon, F., Vietri-Rudan, M., Campello, S., Nazio, F., Florenzano, F., Fimia, G. M., Piacentini, M., Levine, B., & Cecconi, F. (2011). Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy. EMBO Journal, 30(7), 1195-1208. https://doi.org/10.1038/emboj.2011.49