Nutrient-dependent mTORC1 Association with the ULK1–Atg13–FIP200 Complex Required for Autophagy
Top Cited Papers
- 1 April 2009
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 20 (7), 1981-1991
- https://doi.org/10.1091/mbc.e08-12-1248
Abstract
Autophagy is an intracellular degradation system, by which cytoplasmic contents are degraded in lysosomes. Autophagy is dynamically induced by nutrient depletion to provide necessary amino acids within cells, thus helping them adapt to starvation. Although it has been suggested that mTOR is a major negative regulator of autophagy, how it controls autophagy has not yet been determined. Here, we report a novel mammalian autophagy factor, Atg13, which forms a stable ∼3-MDa protein complex with ULK1 and FIP200. Atg13 localizes on the autophagic isolation membrane and is essential for autophagosome formation. In contrast to yeast counterparts, formation of the ULK1–Atg13–FIP200 complex is not altered by nutrient conditions. Importantly, mTORC1 is incorporated into the ULK1–Atg13–FIP200 complex through ULK1 in a nutrient-dependent manner and mTOR phosphorylates ULK1 and Atg13. ULK1 is dephosphorylated by rapamycin treatment or starvation. These data suggest that mTORC1 suppresses autophagy through direct regulation of the ∼3-MDa ULK1–Atg13–FIP200 complex.Keywords
This publication has 55 references indexed in Scilit:
- ULK-Atg13-FIP200 Complexes Mediate mTOR Signaling to the Autophagy MachineryMolecular Biology of the Cell, 2009
- Beclin 1 Forms Two Distinct Phosphatidylinositol 3-Kinase Complexes with Mammalian Atg14 and UVRAGMolecular Biology of the Cell, 2008
- FIP200, a key signaling node to coordinately regulate various cellular processesCellular Signalling, 2008
- FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cellsThe Journal of cell biology, 2008
- Autophagy fights disease through cellular self-digestionNature, 2008
- The Atg1 Kinase Complex Is Involved in the Regulation of Protein Recruitment to Initiate Sequestering Vesicle Formation for Nonspecific Autophagy inSaccharomyces cerevisiaeMolecular Biology of the Cell, 2008
- Autophagy in the Pathogenesis of DiseaseCell, 2008
- Role of FIP200 in cardiac and liver development and its regulation of TNFα and TSC–mTOR signaling pathwaysThe Journal of cell biology, 2006
- Role and Regulation of Starvation-Induced Autophagy in the Drosophila Fat BodyDevelopmental Cell, 2004
- Tor, a Phosphatidylinositol Kinase Homologue, Controls Autophagy in YeastJournal of Biological Chemistry, 1998