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Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy.

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

Authors

  • Strappazzon F
  • Vietri-Rudan M
  • Campello S
  • Nazio F
  • Florenzano F
  • Fimia GM
  • Piacentini M
  • Levine B
  • Cecconi F

Journal

The EMBO journal

Publication Data

April 6, 2011

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:

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