Nutrient-dependent mTORCl association with the ULK1-Atg13-FIP200 complex required for autophagy

Nao Hosokawa, Taichi Hara, Takeshi Kaizuka, Chieko Kishi, Akito Takamura, Yutaka Miura, Shun Ichiro Iemura, Tohru Natsume, Kenji Takehana, Naoyuki Yamada, Jun Lin Guan, Noriko Oshiro, Noboru Mizushima

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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.

Original languageEnglish
Pages (from-to)1981-1991
Number of pages11
JournalMolecular biology of the cell
Volume20
Issue number7
DOIs
Publication statusPublished - 2009 Apr 1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Hosokawa, N., Hara, T., Kaizuka, T., Kishi, C., Takamura, A., Miura, Y., Iemura, S. I., Natsume, T., Takehana, K., Yamada, N., Guan, J. L., Oshiro, N., & Mizushima, N. (2009). Nutrient-dependent mTORCl association with the ULK1-Atg13-FIP200 complex required for autophagy. Molecular biology of the cell, 20(7), 1981-1991. https://doi.org/10.1091/mbc.E08-12-1248