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.

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. - ISSN 1554-8627. - 11:3(2015), pp. 452-459. [10.1080/15548627.2015.1017191]

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

MAIURI, MARIA CHIARA;
2015

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.
2015
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. - ISSN 1554-8627. - 11:3(2015), pp. 452-459. [10.1080/15548627.2015.1017191]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/621046
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