title: Bim inhibits autophagy by recruiting Beclin 1 to microtubules.
abstract: Bim is a proapoptotic BH3-only Bcl-2 family member. In response to death stimuli, Bim dissociates from the dynein light chain 1 (DYNLL1/LC8), where it is inactive, and can then initiate Bax/Bak-mediated mitochondria-dependent apoptosis. We found that Bim depletion increases autophagosome synthesis in cells and in vivo, and this effect is inhibited by overexpression of cell death-deficient Bim. Bim inhibits autophagy by interacting with Beclin 1, an autophagy regulator, and this interaction is facilitated by LC8. Bim bridges the Beclin 1-LC8 interaction and thereby inhibits autophagy by mislocalizing Beclin 1 to the dynein motor complex. Starvation, an autophagic stimulus, induces Bim phosphorylation, which abrogates LC8 binding to Bim, leading to dissociation of Bim and Beclin 1. Our data suggest that Bim switches locations between apoptosis-inactive/autophagy-inhibitory and apoptosis-active/autophagy-permissive sites.
authors: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
authors: Shouqing
authors: S
authors: Luo
authors: Moises
authors: M
authors: Garcia-Arencibia
authors: Rui
authors: R
authors: Zhao
authors: Claudia
authors: C
authors: Puri
authors: Pearl P C
authors: PP
authors: Toh
authors: Oana
authors: O
authors: Sadiq
authors: David C
authors: DC
authors: Rubinsztein
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology*; D000072224:Bcl-2-Like Protein 11; D000071186:Beclin-1; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; C491997:BECN1 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins