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PMID: 23999079 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Review

The beginning of the end: how scaffolds nucleate autophagosome biogenesis.

Trends in cell biology ·Vol. 24 ·No. 1 ·2014-01-00 ·Pages 73-81

Stanley RE, Ragusa MJ, Hurley JH

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.

Keywords
Atg1 Atg13 Atg9 SNAREs ULK1 autophagy membrane bending vesicle tethering
MeSH Terms
Adaptor Proteins, Vesicular Transport/metabolism Animals Autophagy Biological Transport Humans Membrane Fusion Phagosomes/metabolism Transport Vesicles/metabolism Vacuoles/metabolism
Chemicals
Adaptor Proteins, Vesicular Transport
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Stanley Robin E
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Ragusa Michael J
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.
Hurley James H
Department of Molecular and Cell Biology, California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA. Electronic address: jimhurley@berkeley.edu.
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Article Info
Journal
Trends in cell biology
Abbr.
Trends Cell Biol
ISSN
1879-3088
DOI
10.1016/j.tcb.2013.07.008
Email
jimhurley@berkeley.edu
Published
2014-01-00
Epub
2013-00-30
Pages
73-81
Language
English
Region
England
NLM ID
9200566
PMCID
PMC3877172
Subset
IM
Grants
NIGMS NIH HHS · F32 GM099319 · United States
Intramural NIH HHS · ZIA DK075067-01 · United States
NIGMS NIH HHS · GM099319 · United States
External Links
PubMed source DOI: 10.1016/j.tcb.2013.07.008 PMC Full Text View journal details
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