An expanded role for mTORC1 in autophagy

doi:10.1080/23723556.2015.1010958

. 2015 Feb 3;3(1):e1010958.

doi: 10.1080/23723556.2015.1010958. eCollection 2016 Jan.

An expanded role for mTORC1 in autophagy

Young-Mi Kim¹, Ji-Man Park¹, Douglas Grunwald¹, Do-Hyung Kim²

Affiliations

¹ Department of Biochemistry; Molecular Biology, and Biophysics; University of Minnesota ; Minneapolis, MN USA.
² Department of Biochemistry; Molecular Biology, and Biophysics; University of Minnesota; Minneapolis, MN USA; Masonic Cancer Center; University of Minnesota; Minneapolis, MN USA.

PMID: 27308528
PMCID: PMC4845164
DOI: 10.1080/23723556.2015.1010958

An expanded role for mTORC1 in autophagy

Young-Mi Kim et al. Mol Cell Oncol. 2015.

. 2015 Feb 3;3(1):e1010958.

doi: 10.1080/23723556.2015.1010958. eCollection 2016 Jan.

Authors

Young-Mi Kim¹, Ji-Man Park¹, Douglas Grunwald¹, Do-Hyung Kim²

Affiliations

¹ Department of Biochemistry; Molecular Biology, and Biophysics; University of Minnesota ; Minneapolis, MN USA.
² Department of Biochemistry; Molecular Biology, and Biophysics; University of Minnesota; Minneapolis, MN USA; Masonic Cancer Center; University of Minnesota; Minneapolis, MN USA.

PMID: 27308528
PMCID: PMC4845164
DOI: 10.1080/23723556.2015.1010958

Abstract

Mechanistic target of rapamycin complex 1 (mTORC1) negatively regulates autophagy at early stages by phosphorylating Unc51-like kinase 1 (ULK1). Our recent study expanded the roles of mTORC1 in autophagy by identifying ultraviolet radiation resistance-associated gene product (UVRAG) as a substrate of mTORC1. This finding has provided new insight into the roles of mTORC1 in cellular membrane processes and cancer.

Keywords: RUBICON; UVRAG; autophagy; endosome; lysosome; mTOR; mTORC1.

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Figures

**Figure 1.**
mTORC1 suppresses both early and late stages of autophagy. mTORC1 phosphorylates ULK1 and UVRAG to negatively regulate autophagy induction and autophagosome maturation, respectively. mTORC1-mediated phosphorylation of UVRAG also has a negative effect on endosomal maturation and the lysosomal degradation of EGFR.

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References

1. Ganley IG, Lam du H, Wang J, Ding X, Chen S, Jiang X. ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. J Biol Chem 2009; 284:12297-305; PMID:19258318; http://dx.doi.org/10.1074/jbc.M900573200 - DOI - PMC - PubMed
1. Hosokawa N, Hara T, Kaizuka T, Kishi C, Takamura A, Miura Y, Iemura S, Natsume T, Takehana K, Yamada N, et al.. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell 2009; 20:1981-91; PMID:19211835; http://dx.doi.org/10.1091/mbc.E08-12-1248 - DOI - PMC - PubMed
1. Jung CH, Jun CB, Ro SH, Kim YM, Otto NM, Cao J, Kundu M, Kim DH. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell 2009; 20:1992-2003; PMID:19225151; http://dx.doi.org/10.1091/mbc.E08-12-1249 - DOI - PMC - PubMed
1. Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 2011; 13:132-41; PMID:21258367; http://dx.doi.org/10.1038/ncb2152 - DOI - PMC - PubMed
1. Kim Y, Jung CH, Seo M, Kim EK, Park J, Bae SS, Kim DH. mTORC1 Phosphorylates UVRAG to Negatively Regulate Autophagosome and Endosome Maturation. Mol Cell 2014; 57:207-18 - PMC - PubMed

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[1] Ganley IG, Lam du H, Wang J, Ding X, Chen S, Jiang X. ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. J Biol Chem 2009; 284:12297-305; PMID:19258318; http://dx.doi.org/10.1074/jbc.M900573200 - DOI - PMC - PubMed

[2] Ganley IG, Lam du H, Wang J, Ding X, Chen S, Jiang X. ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. J Biol Chem 2009; 284:12297-305; PMID:19258318; http://dx.doi.org/10.1074/jbc.M900573200 - DOI - PMC - PubMed

[3] Hosokawa N, Hara T, Kaizuka T, Kishi C, Takamura A, Miura Y, Iemura S, Natsume T, Takehana K, Yamada N, et al.. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell 2009; 20:1981-91; PMID:19211835; http://dx.doi.org/10.1091/mbc.E08-12-1248 - DOI - PMC - PubMed

[4] Hosokawa N, Hara T, Kaizuka T, Kishi C, Takamura A, Miura Y, Iemura S, Natsume T, Takehana K, Yamada N, et al.. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell 2009; 20:1981-91; PMID:19211835; http://dx.doi.org/10.1091/mbc.E08-12-1248 - DOI - PMC - PubMed

[5] Jung CH, Jun CB, Ro SH, Kim YM, Otto NM, Cao J, Kundu M, Kim DH. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell 2009; 20:1992-2003; PMID:19225151; http://dx.doi.org/10.1091/mbc.E08-12-1249 - DOI - PMC - PubMed

[6] Jung CH, Jun CB, Ro SH, Kim YM, Otto NM, Cao J, Kundu M, Kim DH. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell 2009; 20:1992-2003; PMID:19225151; http://dx.doi.org/10.1091/mbc.E08-12-1249 - DOI - PMC - PubMed

[7] Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 2011; 13:132-41; PMID:21258367; http://dx.doi.org/10.1038/ncb2152 - DOI - PMC - PubMed

[8] Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 2011; 13:132-41; PMID:21258367; http://dx.doi.org/10.1038/ncb2152 - DOI - PMC - PubMed

[9] Kim Y, Jung CH, Seo M, Kim EK, Park J, Bae SS, Kim DH. mTORC1 Phosphorylates UVRAG to Negatively Regulate Autophagosome and Endosome Maturation. Mol Cell 2014; 57:207-18 - PMC - PubMed

[10] Kim Y, Jung CH, Seo M, Kim EK, Park J, Bae SS, Kim DH. mTORC1 Phosphorylates UVRAG to Negatively Regulate Autophagosome and Endosome Maturation. Mol Cell 2014; 57:207-18 - PMC - PubMed

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An expanded role for mTORC1 in autophagy

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An expanded role for mTORC1 in autophagy

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