Author: ["Oliver Florey","Sung Eun Kim","Cynthia P. Sandoval","Cole M. Haynes","Michael Overholtzer"]
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Abstract
Autophagy normally involves the formation of double-membrane autophagosomes that mediate bulk cytoplasmic and organelle degradation. Here we report the modification of single-membrane vacuoles in cells by autophagy proteins. LC3 (Light chain 3) a component of autophagosomes, is recruited to single-membrane entotic vacuoles, macropinosomes and phagosomes harbouring apoptotic cells, in a manner dependent on the lipidation machinery including ATG5 and ATG7, and the class III phosphatidylinositol-3-kinase VPS34. These downstream components of the autophagy machinery, but not the upstream mammalian Tor (mTor)-regulated ULK–ATG13–FIP200 complex, facilitate lysosome fusion to single membranes and the degradation of internalized cargo. For entosis, a live-cell-engulfment program, the autophagy-protein-dependent fusion of lysosomes to vacuolar membranes leads to the death of internalized cells. As pathogen-containing phagosomes can be targeted in a similar manner, the death of epithelial cells by this mechanism mimics pathogen destruction. These data demonstrate that proteins of the autophagy pathway can target single-membrane vacuoles in cells in the absence of pathogenic organisms. An epithelial cell can be engulfed by its neighbour through entosis, which frequently results in the death of the entosed cell. Overholtzer and colleagues show that the autophagy machinery is recruited to single-membrane entotic vacuoles and promotes their fusion with lysosomes. Single-membrane macrophage phagosomes containing apoptotic cells are also targeted for destruction by the autophagy pathway.Cite this article
Florey, O., Kim, S., Sandoval, C. et al. Autophagy machinery mediates macroendocytic processing and entotic cell death by targeting single membranes. Nat Cell Biol 13, 1335–1343 (2011). https://doi.org/10.1038/ncb2363 