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

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.

SUBMITTER: Strappazzon F

PROVIDER: S-EPMC4922440 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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

Strappazzon Flavie F Di Rita Anthea A Cianfanelli Valentina V D'Orazio Melania M Nazio Francesca F Fimia Gian Maria GM Cecconi Francesco F

Autophagy 20160428 6

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 b ...[more]

PMID: 27123694

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