Mechanisms of Autophagy Initiation

By James H. Hurley, Lindsey N. Young. Annual Review of Biochemistry, 2017

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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 protein kinase complex and the PI3KC3-C1 lipid kinase complex. Some 90 % of the mass of these large protein complexes consists on non-catalytic domains and subunits, and the ULK1 complex has essential non-catalytic activities. Structural studies of these complexes have shed increasing light on the regulation of their catalytic and non-catalytic activities in autophagy initiation. The autophagosome is thought to nucleate from vesicles containing the integral membrane protein Atg9, COPII vesicles, and possibly other sources. In the wake of reconstitution and superresolution 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.

Subfields: Cell Biology, Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/bb40f63035d8a14b508fcb89caf4ee82748270d9