title: Diverse autophagosome membrane sources coalesce in recycling endosomes.
abstract: Autophagic protein degradation is mediated by autophagosomes that fuse with lysosomes, where their contents are degraded. The membrane origins of autophagosomes may involve multiple sources. However, it is unclear if and where distinct membrane sources fuse during autophagosome biogenesis. Vesicles containing mATG9, the only transmembrane autophagy protein, are seen in many sites, and fusions with other autophagic compartments have not been visualized in mammalian cells. We observed that mATG9 traffics from the plasma membrane to recycling endosomes in carriers that appear to be routed differently from ATG16L1-containing vesicles, another source of autophagosome membrane. mATG9- and ATG16L1-containing vesicles traffic to recycling endosomes, where VAMP3-dependent heterotypic fusions occur. These fusions correlate with autophagosome formation, and both processes are enhanced by perturbing membrane egress from recycling endosomes. Starvation, a primordial autophagy activator, reduces membrane recycling from recycling endosomes and enhances mATG9-ATG16L1 vesicle fusion. Thus, this mechanism may fine-tune physiological autophagic responses.
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Claudia
authors.initials: C
authors.lastname: Puri
authors.forename: Maurizio
authors.initials: M
authors.lastname: Renna
authors.forename: Carla F
authors.initials: CF
authors.lastname: Bento
authors.forename: Kevin
authors.initials: K
authors.lastname: Moreau
authors.forename: David C
authors.initials: DC
authors.lastname: Rubinsztein
mesh_terms: D000818:Animals; D001343:Autophagy; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D008565:Membrane Proteins
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