BARgaining membranes for autophagosome formation: Regulation of autophagy and tumorigenesis by Bif-1/Endophilin B1.
Autophagy is an intracellular system for the bulk degradation of cytoplasmic components enclosed within double-membrane structures known as autophagosomes. To date, many autophagy-related (Atg) genes have been identified by independent genetic screens for autophagy-defective mutants in yeast; however, the molecular machinery required for the biogenesis of autophagosomes in mammalian systems has yet to be determined.(1,2) Recently, we have reported that Bif-1 interacts with Beclin 1 through UVRAG and promotes the activation of class III phosphatidylinositol 3-kinase (PI3KC3) and the formation of autophagosomes.(3) Moreover, we have found that loss of Bif-1 promotes starvation-induced caspase activation, but prolongs cell survival by suppressing autophagydependent cell death, and enhances spontaneous tumorigenesis in mice. Bif-1 is a member of the endophilin family, which possesses membrane binding and liposome tubulation activities.(4) During nutrient deprivation, Bif-1 accumulates in punctate foci where it co-localizes with LC3, Atg5 and Atg9. Time-lapse microscopy analyses reveal that Bif-1-positive small vesicles expand by recruiting and fusing with Atg9-positive small membranes to form autophagosomes. Taken together, our findings highlight Bif-1 as a potential regulator of autophagosome biogenesis and as a tumor suppressor.
Takahashi
Yoshinori
Y
H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, USA.
Meyerkord
Cheryl L
CL
Wang
Hong-Gang
HG
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D000071183:Autophagy-Related Proteins; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
C434065:ATG9 protein, S cerevisiae; D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; C486100:Sh3glb1 protein, mouse