Prosurvival AMBRA1 turns into a proapoptotic BH3-like protein during mitochondrial apoptosis

Flavie Strappazzon, Anthea Di Rita, V. Cianfanelli, M. D'Orazio, Francesca Nazio, Gian Maria Fimia, Francesco Cecconi

Research output: Contribution to journalArticlepeer-review


ABSTRACT: Autophagy and apoptosis are 2 stress-response mechanisms that are closely interconnected. However, the molecular interplays between these 2 pathways remain to be clarified. Here we report that the crucial proautophagic factor AMBRA1 can act as a positive mediator of mitochondrial apoptosis. Indeed, we show that, in a proapoptotic positive feedback loop, the C-terminal part of AMBRA1, generated by CASP/CASPASE cleavage upon apoptosis induction, inhibits the antiapoptotic factor BCL2 by a direct binding through its BH3-like domain. The mitochondrial AMBRA1-BCL2 complex is thus at the crossroad between autophagy and cell death and may represent a novel target in development of therapeutic approaches in clinical diseases.

Original languageEnglish
Pages (from-to)963-975
Number of pages13
Issue number6
Publication statusPublished - Jun 2 2016


  • AMBRA1
  • apoptosis
  • autophagy
  • BCL2
  • BH3 domain

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology


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