Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy

Joungmok Kim, Young Chul Kim, Chong Fang, Ryan C. Russell, Jeong Hee Kim, Weiliang Fan, Rong Liu, Qing Zhong, Kun Liang Guan

Research output: Contribution to journalArticle

395 Scopus citations

Abstract

Autophagy is a stress response protecting cells from unfavorable conditions, such as nutrient starvation. The class III phosphatidylinositol-3 kinase, Vps34, forms multiple complexes and regulates both intracellular vesicle trafficking and autophagy induction. Here, we show that AMPK plays a key role in regulating different Vps34 complexes. AMPK inhibits the nonautophagy Vps34 complex by phosphorylating T163/S165 in Vps34 and therefore suppresses overall PI(3)P production and protects cells from starvation. In parallel, AMPK activates the proautophagy Vps34 complex by phosphorylating S91/S94 in Beclin1 to induce autophagy. Atg14L, an autophagy-essential gene present only in the proautophagy Vps34 complex, inhibits Vps34 phosphorylation but increases Beclin1 phosphorylation by AMPK. As such, Atg14L dictates the differential regulation (either inhibition or activation) of different Vps34 complexes in response to glucose starvation. Our study reveals an intricate molecular regulation of Vps34 complexes by AMPK in nutrient stress response and autophagy.

Original languageEnglish (US)
Pages (from-to)290-303
Number of pages14
JournalCell
Volume152
Issue number1-2
DOIs
StatePublished - Jan 7 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy'. Together they form a unique fingerprint.

  • Cite this

    Kim, J., Kim, Y. C., Fang, C., Russell, R. C., Kim, J. H., Fan, W., Liu, R., Zhong, Q., & Guan, K. L. (2013). Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy. Cell, 152(1-2), 290-303. https://doi.org/10.1016/j.cell.2012.12.016