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Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy.

The EMBO journal | Apr 6, 2011

http://www.ncbi.nlm.nih.gov/pubmed/21358617

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.

Pubmed ID: 21358617 RIS Download

Mesh terms: Adaptor Proteins, Signal Transducing | Apoptosis Regulatory Proteins | Autophagy | Carrier Proteins | Cell Line | Endoplasmic Reticulum | Gene Expression Regulation | Humans | Membrane Proteins | Mitochondrial Membranes | Protein Interaction Mapping | Proto-Oncogene Proteins c-bcl-2

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Associated grants

  • Agency: NCI NIH HHS, Id: R01 CA109618
  • Agency: NCI NIH HHS, Id: R01 CA109618
  • Agency: Telethon, Id: TCR04004
  • Agency: Howard Hughes Medical Institute, Id:

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