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

Research output: Contribution to journalArticle

592 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

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Autophagy
Phosphotransferases
Lipids
Starvation
Amino Acids
Caenorhabditis elegans
Beclin-1
Mammals
Phosphorylation
Food

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Russell, R. C., Tian, Y., Yuan, H., Park, H. W., Chang, Y. Y., Kim, J., ... 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
Russell, Ryan C. ; Tian, Ye ; Yuan, Haixin ; Park, Hyun Woo ; Chang, Yu Yun ; Kim, Joungmok ; Kim, Haerin ; Neufeld, Thomas P. ; Dillin, Andrew ; Guan, Kun Liang. / ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. In: Nature Cell Biology. 2013 ; Vol. 15, No. 7. pp. 741-750.
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Russell, RC, Tian, Y, Yuan, H, Park, HW, Chang, YY, Kim, J, Kim, H, Neufeld, TP, Dillin, A & Guan, KL 2013, 'ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase', Nature Cell Biology, vol. 15, no. 7, pp. 741-750. https://doi.org/10.1038/ncb2757

ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. / Russell, Ryan C.; Tian, Ye; Yuan, Haixin; Park, Hyun Woo; Chang, Yu Yun; Kim, Joungmok; Kim, Haerin; Neufeld, Thomas P.; Dillin, Andrew; Guan, Kun Liang.

In: Nature Cell Biology, Vol. 15, No. 7, 01.07.2013, p. 741-750.

Research output: Contribution to journalArticle

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