ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase

Ryan C. Russell, Ye Tian, Haixin Yuan, Hyun Woo Park, Yu Yun Chang, Joungmok Kim, Haerin Kim, Thomas P. Neufeld, Andrew Dillin, Kun Liang Guan

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725 Citations (Scopus)

Abstract

Autophagy is the primary cellular catabolic program activated in response to nutrient starvation. Initiation of autophagy, particularly by amino-acid withdrawal, requires the ULK kinases. Despite its pivotal role in autophagy initiation, little is known about the mechanisms by which ULK promotes autophagy. Here we describe a molecular mechanism linking ULK to the pro-autophagic lipid kinase VPS34. Following amino-acid starvation or mTOR inhibition, the activated ULK1 phosphorylates Beclin-1 on Ser 14, thereby enhancing the activity of the ATG14L-containing VPS34 complexes. The Beclin-1 Ser 14 phosphorylation by ULK is required for full autophagic induction in mammals and this requirement is conserved in Caenorhabditis elegans. Our study reveals a molecular link from ULK1 to activation of the autophagy-specific VPS34 complex and autophagy induction.

Original languageEnglish
Pages (from-to)741-750
Number of pages10
JournalNature Cell Biology
Volume15
Issue number7
DOIs
Publication statusPublished - 2013 Jul 1

All Science Journal Classification (ASJC) codes

  • Cell Biology

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    Russell, R. C., Tian, Y., Yuan, H., Park, H. W., Chang, Y. Y., Kim, J., Kim, H., Neufeld, T. P., Dillin, A., & Guan, K. L. (2013). ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. Nature Cell Biology, 15(7), 741-750. https://doi.org/10.1038/ncb2757