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

43 Citations (Scopus)

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

Fingerprint

Autophagy
Peptidomimetics
HCT116 Cells
Colonic Neoplasms
Fibroblasts
Apoptosis
ABT-737

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

BAX and BAK1 are dispensable for ABT-737- induced dissociation of the BCL2-BECN1 complex and autophagy. / Pedro, Jose Manuel Bravo San; Wei, Yongjie; Sica, Valentina; Maiuri, Maria Chiara; Zou, Zhongju; Kroemer, Guido; Levine, Beth.

In: Autophagy, Vol. 11, No. 3, 01.01.2015, p. 452-459.

Research output: Contribution to journalArticle

Pedro, Jose Manuel Bravo San ; Wei, Yongjie ; Sica, Valentina ; Maiuri, Maria Chiara ; Zou, Zhongju ; Kroemer, Guido ; Levine, Beth. / BAX and BAK1 are dispensable for ABT-737- induced dissociation of the BCL2-BECN1 complex and autophagy. In: Autophagy. 2015 ; Vol. 11, No. 3. pp. 452-459.
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