title: Mechanisms of Autophagy Initiation.
abstract: Autophagy is the process of cellular self-eating by a double-membrane organelle, the autophagosome. A range of signaling processes converge on two protein complexes to initiate autophagy: the ULK1 (unc51-like autophagy activating kinase 1) protein kinase complex and the PI3KC3-C1 (class III phosphatidylinositol 3-kinase complex I) lipid kinase complex. Some 90% of the mass of these large protein complexes consists of noncatalytic domains and subunits, and the ULK1 complex has essential noncatalytic activities. Structural studies of these complexes have shed increasing light on the regulation of their catalytic and noncatalytic activities in autophagy initiation. The autophagosome is thought to nucleate from vesicles containing the integral membrane protein Atg9 (autophagy-related 9), COPII (coat protein complex II) vesicles, and possibly other sources. In the wake of reconstitution and super-resolution imaging studies, we are beginning to understand how the ULK1 and PI3KC3-C1 complexes might coordinate the nucleation and fusion of Atg9 and COPII vesicles at the start of autophagosome biogenesis.
authors.affiliation: Department of Molecular and Cell Biology and California Institute of Quantitative Biosciences, University of California, Berkeley, California, and Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720; email: jimhurley@berkeley.edu.
authors.forename: James H
authors.initials: JH
authors.lastname: Hurley
authors.affiliation: Department of Molecular and Cell Biology and California Institute of Quantitative Biosciences, University of California, Berkeley, California, and Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720; email: jimhurley@berkeley.edu.
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Young
mesh_terms: D001343:Autophagy / Q000235:genetics*; D000071189:Autophagy-Related Protein-1 Homolog / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D022181:COP-Coated Vesicles / Q000378:metabolism / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D058546:Class III Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000378:metabolism / Q000648:ultrastructure; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism* / Q000648:ultrastructure; D058539:Phosphatidylinositol 3-Kinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D015398:Signal Transduction
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D058546:Class III Phosphatidylinositol 3-Kinases; D058539:Phosphatidylinositol 3-Kinase; D000071189:Autophagy-Related Protein-1 Homolog; C484754:ULK1 protein, human
keywords: Atg1; COPII; ULK1; Vps34; membrane fusion; membrane remodeling; nanoscale biology; phosphatidylinositol 3-kinase; tethering complex; vesicle