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.

Strappazzon, F., Di Rita, A., Cianfanelli, V., D'Orazio, M., Nazio, F., Fimia, G.M., et al. (2016). Prosurvival AMBRA1 turns into a proapoptotic BH3-like protein during mitochondrial apoptosis. AUTOPHAGY, 12(6), 963-975 [10.1080/15548627.2016.1164359].

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

Cianfanelli V.;Nazio F.;
2016-01-01

Abstract

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.
2016
Strappazzon, F., Di Rita, A., Cianfanelli, V., D'Orazio, M., Nazio, F., Fimia, G.M., et al. (2016). Prosurvival AMBRA1 turns into a proapoptotic BH3-like protein during mitochondrial apoptosis. AUTOPHAGY, 12(6), 963-975 [10.1080/15548627.2016.1164359].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11590/469172
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