Autophagy machinery mediates macroendocytic processing and entotic cell death by targeting single membranes

Oliver Florey, Sung Eun Kim, Cynthia P. Sandoval, Cole M. Haynes, Michael Overholtzer

Research output: Contribution to journalArticlepeer-review

278 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1335-1343
Number of pages9
JournalNature Cell Biology
Volume13
Issue number11
DOIs
Publication statusPublished - 2011 Nov
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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