Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy

Research output: Contribution to journalArticle

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
Pages (from-to)1195-1208
Number of pages14
JournalEMBO Journal
Volume30
Issue number7
DOIs
Publication statusPublished - Apr 6 2011

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Autophagy
Apoptosis
Mitochondria
Proteins
Endoplasmic Reticulum

Keywords

  • apoptosis
  • autophagy
  • endoplasmic reticulum
  • mitochondria

ASJC Scopus subject areas

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

Cite this

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, Vol. 30, No. 7, 06.04.2011, p. 1195-1208.

Research output: Contribution to journalArticle

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