ULK1/2 Constitute a Bifurcate Node Controlling Glucose Metabolic Fluxes in Addition to Autophagy

Terytty Yang Li; Yu Sun; Yu Liang; Qing Liu; Yuzhe Shi; Chen Song Zhang; Cixiong Zhang; Lintao Song; Pu Zhang; Xianzhong Zhang; Xiaotong Li; Tao Chen; Hui Ying Huang; Xiadi He; Yi Wang; Yu Qing Wu; Shaoxuan Chen; Ming Jiang; Canhe Chen; Changchuan Xie; James Y. Yang; Yan Lin; Shimin Zhao; Zhiyun Ye; Shu Yong Lin; Daniel Tsun Yee Chiu; Sheng Cai Lin

doi:10.1016/j.molcel.2016.04.009

ULK1/2 Constitute a Bifurcate Node Controlling Glucose Metabolic Fluxes in Addition to Autophagy

Terytty Yang Li, Yu Sun, Yu Liang, Qing Liu, Yuzhe Shi, Chen Song Zhang, Cixiong Zhang, Lintao Song, Pu Zhang, Xianzhong Zhang, Xiaotong Li, Tao Chen, Hui Ying Huang, Xiadi He, Yi Wang, Yu Qing Wu, Shaoxuan Chen, Ming Jiang, Canhe Chen, Changchuan XieJames Y. Yang, Yan Lin, Shimin Zhao, Zhiyun Ye, Shu Yong Lin, Daniel Tsun Yee Chiu, Sheng Cai Lin^*

^*Corresponding author for this work

Department of Medical Biotechnology and Laboratory Science

Research output: Contribution to journal › Journal Article › peer-review

87 Scopus citations

Abstract

Metabolic reprogramming is fundamental to biological homeostasis, enabling cells to adjust metabolic routes after sensing altered availability of fuels and growth factors. ULK1 and ULK2 represent key integrators that relay metabolic stress signals to the autophagy machinery. Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1). Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels. These results identify ULK1/2 as a bifurcate-signaling node that sustains glucose metabolic fluxes besides initiation of autophagy in response to nutritional deprivation.

Original language	English
Pages (from-to)	359-370
Number of pages	12
Journal	Molecular Cell
Volume	62
Issue number	3
DOIs	https://doi.org/10.1016/j.molcel.2016.04.009
State	Published - 05 05 2016

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© 2016 Elsevier Inc..

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Li, T. Y., Sun, Y., Liang, Y., Liu, Q., Shi, Y., Zhang, C. S., Zhang, C., Song, L., Zhang, P., Zhang, X., Li, X., Chen, T., Huang, H. Y., He, X., Wang, Y., Wu, Y. Q., Chen, S., Jiang, M., Chen, C., ... Lin, S. C. (2016). ULK1/2 Constitute a Bifurcate Node Controlling Glucose Metabolic Fluxes in Addition to Autophagy. Molecular Cell, 62(3), 359-370. https://doi.org/10.1016/j.molcel.2016.04.009

@article{e85e613b8e854d21bdb5c0540f7912c9,

title = "ULK1/2 Constitute a Bifurcate Node Controlling Glucose Metabolic Fluxes in Addition to Autophagy",

abstract = "Metabolic reprogramming is fundamental to biological homeostasis, enabling cells to adjust metabolic routes after sensing altered availability of fuels and growth factors. ULK1 and ULK2 represent key integrators that relay metabolic stress signals to the autophagy machinery. Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1). Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels. These results identify ULK1/2 as a bifurcate-signaling node that sustains glucose metabolic fluxes besides initiation of autophagy in response to nutritional deprivation.",

author = "Li, {Terytty Yang} and Yu Sun and Yu Liang and Qing Liu and Yuzhe Shi and Zhang, {Chen Song} and Cixiong Zhang and Lintao Song and Pu Zhang and Xianzhong Zhang and Xiaotong Li and Tao Chen and Huang, {Hui Ying} and Xiadi He and Yi Wang and Wu, {Yu Qing} and Shaoxuan Chen and Ming Jiang and Canhe Chen and Changchuan Xie and Yang, {James Y.} and Yan Lin and Shimin Zhao and Zhiyun Ye and Lin, {Shu Yong} and Chiu, {Daniel Tsun Yee} and Lin, {Sheng Cai}",

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Inc..",

year = "2016",

month = may,

day = "5",

doi = "10.1016/j.molcel.2016.04.009",

language = "英语",

volume = "62",

pages = "359--370",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

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Li, TY, Sun, Y, Liang, Y, Liu, Q, Shi, Y, Zhang, CS, Zhang, C, Song, L, Zhang, P, Zhang, X, Li, X, Chen, T, Huang, HY, He, X, Wang, Y, Wu, YQ, Chen, S, Jiang, M, Chen, C, Xie, C, Yang, JY, Lin, Y, Zhao, S, Ye, Z, Lin, SY, Chiu, DTY & Lin, SC 2016, 'ULK1/2 Constitute a Bifurcate Node Controlling Glucose Metabolic Fluxes in Addition to Autophagy', Molecular Cell, vol. 62, no. 3, pp. 359-370. https://doi.org/10.1016/j.molcel.2016.04.009

TY - JOUR

T1 - ULK1/2 Constitute a Bifurcate Node Controlling Glucose Metabolic Fluxes in Addition to Autophagy

AU - Li, Terytty Yang

AU - Sun, Yu

AU - Liang, Yu

AU - Liu, Qing

AU - Shi, Yuzhe

AU - Zhang, Chen Song

AU - Zhang, Cixiong

AU - Song, Lintao

AU - Zhang, Pu

AU - Zhang, Xianzhong

AU - Li, Xiaotong

AU - Chen, Tao

AU - Huang, Hui Ying

AU - He, Xiadi

AU - Wang, Yi

AU - Wu, Yu Qing

AU - Chen, Shaoxuan

AU - Jiang, Ming

AU - Chen, Canhe

AU - Xie, Changchuan

AU - Yang, James Y.

AU - Lin, Yan

AU - Zhao, Shimin

AU - Ye, Zhiyun

AU - Lin, Shu Yong

AU - Chiu, Daniel Tsun Yee

AU - Lin, Sheng Cai

PY - 2016/5/5

Y1 - 2016/5/5

N2 - Metabolic reprogramming is fundamental to biological homeostasis, enabling cells to adjust metabolic routes after sensing altered availability of fuels and growth factors. ULK1 and ULK2 represent key integrators that relay metabolic stress signals to the autophagy machinery. Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1). Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels. These results identify ULK1/2 as a bifurcate-signaling node that sustains glucose metabolic fluxes besides initiation of autophagy in response to nutritional deprivation.

AB - Metabolic reprogramming is fundamental to biological homeostasis, enabling cells to adjust metabolic routes after sensing altered availability of fuels and growth factors. ULK1 and ULK2 represent key integrators that relay metabolic stress signals to the autophagy machinery. Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1). Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels. These results identify ULK1/2 as a bifurcate-signaling node that sustains glucose metabolic fluxes besides initiation of autophagy in response to nutritional deprivation.

UR - http://www.scopus.com/inward/record.url?scp=84966495117&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2016.04.009

DO - 10.1016/j.molcel.2016.04.009

M3 - 文章

C2 - 27153534

AN - SCOPUS:84966495117

SN - 1097-2765

VL - 62

SP - 359

EP - 370

JO - Molecular Cell

JF - Molecular Cell

IS - 3

ER -

ULK1/2 Constitute a Bifurcate Node Controlling Glucose Metabolic Fluxes in Addition to Autophagy

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