Prosurvival AMBRA1 turns into a proapoptotic BH3-like protein during mitochondrial apoptosis. Issue 6 (2nd June 2016)

• Record Type: Journal Article
• Authors: Strappazzon, Flavie; Di Rita, Anthea; Cianfanelli, Valentina; D'Orazio, Melania; Nazio, Francesca; Fimia, Gian Maria; Cecconi, Francesco
• Is Part Of: Autophagy. Volume 12:Issue 6(2016)
• Page Start: 963
• Page End: 975
• Publication Date: 2016-06-02
• Subjects: AMBRA1 -- apoptosis -- autophagy -- BCL2 -- BH3 domain; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2016.1164359
• Languages: English
• ISSNs: 1554-8627

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.