Mammalian Atg2 proteins are essential for autophagosome formation and important for regulation of size and distribution of lipid droplets
Open Access
- 1 March 2012
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 23 (5), 896-909
- https://doi.org/10.1091/mbc.e11-09-0785
Abstract
Macroautophagy is an intracellular degradation system by which cytoplasmic materials are enclosed by the autophagosome and delivered to the lysosome. Autophagosome formation is considered to take place on the endoplasmic reticulum and involves functions of autophagy-related (Atg) proteins. Here, we report the identification and characterization of mammalian Atg2 homologues Atg2A and Atg2B. Simultaneous silencing of Atg2A and Atg2B causes a block in autophagic flux and accumulation of unclosed autophagic structures containing most Atg proteins. Atg2A localizes on the autophagic membrane, as well as on the surface of lipid droplets. The Atg2A region containing amino acids 1723–1829, which shows relatively high conservation among species, is required for localization to both the autophagic membrane and lipid droplet and is also essential for autophagy. Depletion of both Atg2A and Atg2B causes clustering of enlarged lipid droplets in an autophagy-independent manner. These data suggest that mammalian Atg2 proteins function both in autophagosome formation and regulation of lipid droplet morphology and dispersion.Keywords
This publication has 57 references indexed in Scilit:
- A Conserved SREBP-1/Phosphatidylcholine Feedback Circuit Regulates Lipogenesis in MetazoansCell, 2011
- The WD40 Repeat PtdIns(3)P-Binding Protein EPG-6 Regulates Progression of Omegasomes to AutophagosomesDevelopmental Cell, 2011
- Network organization of the human autophagy systemNature, 2010
- Role of autophagy in suppression of inflammation and cancerCurrent Opinion in Cell Biology, 2010
- Endoplasmic Reticulum Stress and the Inflammatory Basis of Metabolic DiseaseCell, 2010
- Peripheral ER structure and functionCurrent Opinion in Cell Biology, 2009
- The life of lipid dropletsBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2009
- Autophagy, Immunity, and Microbial AdaptationsCell Host & Microbe, 2009
- The Role of Autophagy in Mammalian Development: Cell Makeover Rather than Cell DeathDevelopmental Cell, 2008
- The role of autophagy during the early neonatal starvation periodNature, 2004