Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy
Open Access
- 25 February 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 30 (7), 1195-1208
- https://doi.org/10.1038/emboj.2011.49
Abstract
BECLIN 1 is a central player in macroautophagy. AMBRA1, a BECLIN 1‐interacting protein, positively regulates the BECLIN 1‐dependent programme of autophagy. In this study, we show that AMBRA1 binds preferentially the mitochondrial pool of the antiapoptotic factor BCL‐2, and that this interaction is disrupted following autophagy induction. Further, AMBRA1 can compete with both mitochondrial and endoplasmic reticulum‐resident BCL‐2 (mito‐BCL‐2 and ER‐BCL‐2, respectively) to bind BECLIN 1. Moreover, after autophagy induction, AMBRA1 is recruited to BECLIN 1. Altogether, these results indicate that, in normal conditions, a pool of AMBRA1 binds preferentially mito‐BCL‐2; after autophagy induction, AMBRA1 is released from BCL‐2, consistent with its ability to promote BECLIN 1 activity. In addition, we found that the binding between AMBRA1 and mito‐BCL‐2 is reduced during apoptosis. Thus, a dynamic interaction exists between AMBRA1 and BCL‐2 at the mitochondria that could regulate both BECLIN 1‐dependent autophagy and apoptosis. There is a [Have you seen?][1] (April 2011) associated with this Article. [1]: http://dx.doi.org/10.1038/emboj.2011.75Keywords
This publication has 53 references indexed in Scilit:
- Mitochondria Supply Membranes for Autophagosome Biogenesis during StarvationCell, 2010
- The Beclin 1 interactomeCurrent Opinion in Cell Biology, 2010
- The role of the Atg1/ULK1 complex in autophagy regulationCurrent Opinion in Cell Biology, 2010
- Methods in Mammalian Autophagy ResearchCell, 2010
- Antagonism of Beclin 1-dependent autophagy by BCL-2 at the endoplasmic reticulum requires NAF-1The EMBO Journal, 2009
- Apoptosis blocks Beclin 1-dependent autophagosome synthesis: an effect rescued by Bcl-xLCell Death & Differentiation, 2009
- Bif-1/Endophilin B1: a candidate for crescent driving force in autophagyCell Death & Differentiation, 2009
- JNK1-Mediated Phosphorylation of Bcl-2 Regulates Starvation-Induced AutophagyMolecular Cell, 2008
- Bcl-2-regulated apoptosis: mechanism and therapeutic potentialCurrent Opinion in Immunology, 2007
- Cell DeathCell, 2004