BAX and BAK1 are dispensable for ABT-737- induced dissociation of the BCL2-BECN1 complex and autophagy

Jose Manuel Bravo San Pedro, Yongjie Wei, Valentina Sica, Maria Chiara Maiuri, Zhongju Zou, Guido Kroemer, Beth Levine

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Disruption of the complex of BECN1 with BCL2 or BCL2L1/BCL-XL is an essential switch that turns on cellular autophagy in response to environmental stress or treatment with BH3 peptidomimetics. Recently, it has been proposed that BCL2 and BCL2L1/BCL-XL may inhibit autophagy indirectly through a mechanism dependent on the proapoptotic BCL2 family members, BAX and BAK1. Here we report that the BH3 mimetic, ABT-737, induces autophagy in parallel with disruption of BCL2-BECN1 binding in 2 different apoptosis-deficient cell types lacking BAX and BAK1, namely in mouse embryonic fibroblasts cells and in human colon cancer HCT116 cells. We conclude that the BH3 mimetic ABT- 737 induces autophagy through a BAX and BAK1-independent mechanism that likely involves disruption of BECN1 binding to antiapoptotic BCL2 family members.

Original languageEnglish (US)
Pages (from-to)452-459
Number of pages8
JournalAutophagy
Volume11
Issue number3
DOIs
StatePublished - Jan 1 2015

Keywords

  • ABT-737
  • Apoptosis
  • Autophagy
  • BAK1
  • BAX
  • BCL2
  • BECN1 (Beclin 1)

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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