Autophagy machinery mediates macroendocytic processing and entotic cell death by targeting single membranes Journal Article
| Authors: | Florey, O.; Kim, S. E.; Sandoval, C. P.; Haynes, C. M.; Overholtzer, M. |
| Article Title: | Autophagy machinery mediates macroendocytic processing and entotic cell death by targeting single membranes |
| 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. © 2011 Macmillan Publishers Limited. All rights reserved. |
| Keywords: | controlled study; unclassified drug; nonhuman; animal cell; mammalia; cell survival; apoptosis; embryo; cell protein; embryo development; rna interference; cell line, tumor; transfection; phosphatidylinositol 3 kinase; time factors; regulatory mechanism; mammalian target of rapamycin; cell membrane; epithelium cell; caenorhabditis elegans; autophagy; ubiquitin-activating enzymes; endocytosis; protein atg13; phagosome; proto-oncogene proteins c-bcl-2; cell activity; internalization; lysosome; lysosomes; cell vacuole; microtubule-associated proteins; intracellular membranes; membrane fusion; papillomavirus e7 proteins; entosis; autophagosome; vacuoles; protein atg7; macroendocytic processing; autophagy protein 5; protein fip200; protein ulk; class iii phosphatidylinositol 3-kinases |
| Journal Title: | Nature Cell Biology |
| Volume: | 13 |
| Issue: | 11 |
| ISSN: | 1465-7392 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2011-10-16 |
| Start Page: | 1335 |
| End Page: | 1343 |
| Language: | English |
| DOI: | 10.1038/ncb2363 |
| PROVIDER: | scopus |
| PMCID: | PMC3223412 |
| PUBMED: | 22002674 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 9 December 2011" - "CODEN: NCBIF" - "Source: Scopus" |
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