title: The beginning of the end: how scaffolds nucleate autophagosome biogenesis.
abstract: Autophagy is a conserved mechanism that is essential for cell survival in starvation. Moreover, autophagy maintains cellular health by clearing unneeded or harmful materials from cells. Autophagy proceeds by the engulfment of bulk cytosol and organelles by a cup-shaped double-membrane sheet known as the phagophore. The phagophore closes on itself to form the autophagosome, which delivers its contents to the vacuole or lysosome for degradation. A multiprotein complex comprising the protein kinase autophagy-related protein 1 (Atg1) together with Atg13, Atg17, Atg29, and Atg31 (ULK1, ATG13, FIP200, and ATG101 in humans) has a pivotal role in the earliest steps of this process. This review summarizes recent structural and ultrastructural analysis of the earliest step in autophagosome biogenesis and discusses a model in which the Atg1 complex clusters high-curvature vesicles containing the integral membrane protein Atg9, thereby initiating the phagophore.
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Robin E
authors.initials: RE
authors.lastname: Stanley
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Molecular and Cell Biology, California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ragusa
authors.affiliation: Department of Molecular and Cell Biology, California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA. Electronic address: jimhurley@berkeley.edu.
authors.forename: James H
authors.initials: JH
authors.lastname: Hurley
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D001692:Biological Transport; D006801:Humans; D008561:Membrane Fusion; D010588:Phagosomes / Q000378:metabolism*; D022161:Transport Vesicles / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport
keywords: Atg1; Atg13; Atg9; SNAREs; ULK1; autophagy; membrane bending; vesicle tethering