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

124 Citations (Scopus)

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

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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

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

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

Strappazzon, F, Vietri-Rudan, M, Campello, S, Nazio, F, Florenzano, F, Fimia, GM, Piacentini, M, Levine, B & Cecconi, F 2011, 'Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy', EMBO Journal, vol. 30, no. 7, pp. 1195-1208. https://doi.org/10.1038/emboj.2011.49
Strappazzon F, Vietri-Rudan M, Campello S, Nazio F, Florenzano F, Fimia GM et al. Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy. EMBO Journal. 2011 Apr 6;30(7):1195-1208. https://doi.org/10.1038/emboj.2011.49
Strappazzon, Flavie ; Vietri-Rudan, Matteo ; Campello, Silvia ; Nazio, Francesca ; Florenzano, Fulvio ; Fimia, Gian Maria ; Piacentini, Mauro ; Levine, Beth ; Cecconi, Francesco. / Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy. In: EMBO Journal. 2011 ; Vol. 30, No. 7. pp. 1195-1208.
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