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

361 Citations (Scopus)

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

Fingerprint

AMP-Activated Protein Kinases
Autophagy
Nutrients
Food
Starvation
Phosphorylation
Class III Phosphatidylinositol 3-Kinases
Essential Genes
Genes
Chemical activation
Glucose

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Kim, J., Kim, Y. C., Fang, C., Russell, R. C., Kim, J. H., Fan, W., ... 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

Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy. / Kim, Joungmok; Kim, Young Chul; Fang, Chong; Russell, Ryan C.; Kim, Jeong Hee; Fan, Weiliang; Liu, Rong; Zhong, Qing; Guan, Kun Liang.

In: Cell, Vol. 152, No. 1-2, 07.01.2013, p. 290-303.

Research output: Contribution to journalArticle

Kim, J, Kim, YC, Fang, C, Russell, RC, Kim, JH, Fan, W, Liu, R, Zhong, Q & Guan, KL 2013, 'Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy', Cell, vol. 152, no. 1-2, pp. 290-303. https://doi.org/10.1016/j.cell.2012.12.016
Kim, Joungmok ; Kim, Young Chul ; Fang, Chong ; Russell, Ryan C. ; Kim, Jeong Hee ; Fan, Weiliang ; Liu, Rong ; Zhong, Qing ; Guan, Kun Liang. / Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy. In: Cell. 2013 ; Vol. 152, No. 1-2. pp. 290-303.
@article{ef958969b53b448ea37ce6fa58212b72,
title = "Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy",
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.",
author = "Joungmok Kim and Kim, {Young Chul} and Chong Fang and Russell, {Ryan C.} and Kim, {Jeong Hee} and Weiliang Fan and Rong Liu and Qing Zhong and Guan, {Kun Liang}",
year = "2013",
month = "1",
day = "7",
doi = "10.1016/j.cell.2012.12.016",
language = "English (US)",
volume = "152",
pages = "290--303",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "1-2",

}

TY - JOUR

T1 - Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy

AU - Kim, Joungmok

AU - Kim, Young Chul

AU - Fang, Chong

AU - Russell, Ryan C.

AU - Kim, Jeong Hee

AU - Fan, Weiliang

AU - Liu, Rong

AU - Zhong, Qing

AU - Guan, Kun Liang

PY - 2013/1/7

Y1 - 2013/1/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84872586081&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872586081&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2012.12.016

DO - 10.1016/j.cell.2012.12.016

M3 - Article

C2 - 23332761

AN - SCOPUS:84872586081

VL - 152

SP - 290

EP - 303

JO - Cell

JF - Cell

SN - 0092-8674

IS - 1-2

ER -