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      AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1.

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          Abstract

          Autophagy is a process by which components of the cell are degraded to maintain essential activity and viability in response to nutrient limitation. Extensive genetic studies have shown that the yeast ATG1 kinase has an essential role in autophagy induction. Furthermore, autophagy is promoted by AMP activated protein kinase (AMPK), which is a key energy sensor and regulates cellular metabolism to maintain energy homeostasis. Conversely, autophagy is inhibited by the mammalian target of rapamycin (mTOR), a central cell-growth regulator that integrates growth factor and nutrient signals. Here we demonstrate a molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1. Under glucose starvation, AMPK promotes autophagy by directly activating Ulk1 through phosphorylation of Ser 317 and Ser 777. Under nutrient sufficiency, high mTOR activity prevents Ulk1 activation by phosphorylating Ulk1 Ser 757 and disrupting the interaction between Ulk1 and AMPK. This coordinated phosphorylation is important for Ulk1 in autophagy induction. Our study has revealed a signalling mechanism for Ulk1 regulation and autophagy induction in response to nutrient signalling.

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          Author and article information

          Journal
          Nat Cell Biol
          Nature cell biology
          Springer Science and Business Media LLC
          1476-4679
          1465-7392
          Feb 2011
          : 13
          : 2
          Affiliations
          [1 ] Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92130, USA.
          Article
          NIHMS564121 ncb2152
          10.1038/ncb2152
          3987946
          21258367
          c3a41b4d-4f04-4854-b94e-902e7882bf74
          History

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