[PDF][PDF] Bim inhibits autophagy by recruiting Beclin 1 to microtubules

S Luo, M Garcia-Arencibia, R Zhao, C Puri, PPC Toh… - Molecular cell, 2012 - cell.com
S Luo, M Garcia-Arencibia, R Zhao, C Puri, PPC Toh, O Sadiq, DC Rubinsztein
Molecular cell, 2012cell.com
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 …
Summary
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.
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