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.
Prosurvival AMBRA1 turns into a proapoptotic BH3-like protein during mitochondrial apoptosis / Strappazzon, Flavie; Di Rita, Anthea; Cianfanelli, Valentina; D'Orazio, Melania; Nazio, Francesca; Fimia, Gian Maria; Cecconi, Francesco. - In: AUTOPHAGY. - ISSN 1554-8627. - 12:(2016), pp. 963-975. [10.1080/15548627.2016.1164359]
Prosurvival AMBRA1 turns into a proapoptotic BH3-like protein during mitochondrial apoptosis
FIMIA, Gian Maria;
2016
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.File | Dimensione | Formato | |
---|---|---|---|
Fimia_Prosurvival-AMBRA1.pdf
accesso aperto
Tipologia:
Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza:
Creative commons
Dimensione
2.22 MB
Formato
Adobe PDF
|
2.22 MB | Adobe PDF |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.