title: BCL2 and related prosurvival proteins require BAK1 and BAX to affect autophagy.
abstract: It is widely thought that prosurvival BCL2 family members not only inhibit apoptosis, but also block autophagy by directly binding to BECN1/Beclin 1. To distinguish whether BCL2, BCL2L1/BCL-XL, or MCL1 influence autophagy directly, or indirectly, through their effects on apoptosis, we compared normal cells to those lacking BAX and BAK1. In cells able to undergo mitochondria-mediated apoptosis, inhibiting the endogenous prosurvival BCL2 family members induces both autophagy and cell death, but when BAX and BAK1 are deleted, neither inhibiting nor overexpressing BCL2, BCL2L1, or MCL1 causes any detectable effect on LC3B lipidation, LC3B turnover, or autolysosome formation. These results show that prosurvival BCL2 family members influence autophagy only indirectly, by inhibiting activation of BAX and BAK1.
authors.affiliation: Cell Signalling and Cell Death Division; Walter and Eliza Hall Institute of Medical Research; Melbourne, Victoria Australia; Department of Medical Biology; University of Melbourne; Parkville, Victoria Australia.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Lindqvist
authors.affiliation: Cell Signalling and Cell Death Division; Walter and Eliza Hall Institute of Medical Research; Melbourne, Victoria Australia; Department of Medical Biology; University of Melbourne; Parkville, Victoria Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Vaux
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D002470:Cell Survival; D004331:Drosophila melanogaster / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein
keywords: BAK1; BAX; BCL-XL; BCL2; BCL2L1; BECN1; Beclin 1; LC3B; MCL1; apoptosis; autophagy