PMID- 27153534
OWN - NLM
STAT- MEDLINE
DCOM- 20170802
LR  - 20220409
IS  - 1097-4164 (Electronic)
IS  - 1097-2765 (Linking)
VI  - 62
IP  - 3
DP  - 2016 May 5
TI  - ULK1/2 Constitute a Bifurcate Node Controlling Glucose Metabolic Fluxes in 
      Addition to Autophagy.
PG  - 359-370
LID - S1097-2765(16)30059-4 [pii]
LID - 10.1016/j.molcel.2016.04.009 [doi]
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.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Li, Terytty Yang
AU  - Li TY
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, 
      China.
FAU - Sun, Yu
AU  - Sun Y
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, 
      China.
FAU - Liang, Yu
AU  - Liang Y
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, 
      China.
FAU - Liu, Qing
AU  - Liu Q
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, 
      China.
FAU - Shi, Yuzhe
AU  - Shi Y
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, 
      China.
FAU - Zhang, Chen-Song
AU  - Zhang CS
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, 
      China.
FAU - Zhang, Cixiong
AU  - Zhang C
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, 
      China.
FAU - Song, Lintao
AU  - Song L
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, 
      China.
FAU - Zhang, Pu
AU  - Zhang P
AD  - Center for Molecular Imaging and Translational Medicine, State Key Laboratory of 
      Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen 
      University, Fujian 361102, China.
FAU - Zhang, Xianzhong
AU  - Zhang X
AD  - Center for Molecular Imaging and Translational Medicine, State Key Laboratory of 
      Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen 
      University, Fujian 361102, China.
FAU - Li, Xiaotong
AU  - Li X
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, 
      China.
FAU - Chen, Tao
AU  - Chen T
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, 
      China.
FAU - Huang, Hui-Ying
AU  - Huang HY
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, 
      China.
FAU - He, Xiadi
AU  - He X
AD  - State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan 
      University, Shanghai 200032, China.
FAU - Wang, Yi
AU  - Wang Y
AD  - Institutes of Biomedical Science, Fudan University, Shanghai 200032, China.
FAU - Wu, Yu-Qing
AU  - Wu YQ
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, 
      China.
FAU - Chen, Shaoxuan
AU  - Chen S
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, 
      China.
FAU - Jiang, Ming
AU  - Jiang M
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, 
      China.
FAU - Chen, Canhe
AU  - Chen C
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, 
      China.
FAU - Xie, Changchuan
AU  - Xie C
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, 
      China.
FAU - Yang, James Y
AU  - Yang JY
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, 
      China.
FAU - Lin, Yan
AU  - Lin Y
AD  - State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan 
      University, Shanghai 200032, China.
FAU - Zhao, Shimin
AU  - Zhao S
AD  - State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan 
      University, Shanghai 200032, China.
FAU - Ye, Zhiyun
AU  - Ye Z
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, 
      China.
FAU - Lin, Shu-Yong
AU  - Lin SY
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, 
      China.
FAU - Chiu, Daniel Tsun-Yee
AU  - Chiu DT
AD  - Department of Medical Biotechnology and Laboratory Science, College of Medicine, 
      Chang Gung University, Kwei-san, Tao-yuan 333, Taiwan; Department of Laboratory 
      Medicine, Chang Gung Memorial Hospital, Tau-yuan 333, Taiwan.
FAU - Lin, Sheng-Cai
AU  - Lin SC
AD  - State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell 
      Signaling Network, School of Life Sciences, Xiamen University, Fujian 361102, 
      China. Electronic address: linsc@xmu.edu.cn.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Cell
JT  - Molecular cell
JID - 9802571
RN  - 0 (Amino Acids)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.1.1 (HK1 protein, human)
RN  - EC 2.7.1.1 (HK1 protein, mouse)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.1.11 (Phosphofructokinase-1)
RN  - EC 2.7.1.11 (Ulk2 protein, mouse)
RN  - EC 2.7.11.1 (Autophagy-Related Protein-1 Homolog)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (ULK1 protein, human)
RN  - EC 2.7.11.1 (Ulk1 protein, mouse)
RN  - EC 2.7.11.1 (Ulk2 protein, human)
RN  - EC 3.1.3.11 (Fructose-Bisphosphatase)
RN  - EC 4.2.1.11 (ENO1 protein, human)
RN  - EC 4.2.1.11 (Eno1 protein, mouse)
RN  - EC 4.2.1.11 (Phosphopyruvate Hydratase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Amino Acids/deficiency/metabolism
MH  - Animals
MH  - *Autophagy
MH  - Autophagy-Related Protein-1 Homolog/deficiency/genetics/*metabolism
MH  - Biomarkers, Tumor/metabolism
MH  - Cell Death
MH  - DNA-Binding Proteins/metabolism
MH  - Female
MH  - Fructose-Bisphosphatase/metabolism
MH  - Genotype
MH  - Glucose/*metabolism
MH  - *Glycolysis
MH  - HCT116 Cells
MH  - Hexokinase/metabolism
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - MCF-7 Cells
MH  - Male
MH  - Mice, Knockout
MH  - *Pentose Phosphate Pathway
MH  - Phenotype
MH  - Phosphofructokinase-1/metabolism
MH  - Phosphopyruvate Hydratase/metabolism
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/deficiency/genetics/*metabolism
MH  - RNA Interference
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction
MH  - *Stress, Physiological
MH  - Time Factors
MH  - Transfection
MH  - Tumor Suppressor Proteins/metabolism
EDAT- 2016/05/08 06:00
MHDA- 2017/08/03 06:00
CRDT- 2016/05/07 06:00
PHST- 2015/10/12 00:00 [received]
PHST- 2016/03/09 00:00 [revised]
PHST- 2016/04/05 00:00 [accepted]
PHST- 2016/05/07 06:00 [entrez]
PHST- 2016/05/08 06:00 [pubmed]
PHST- 2017/08/03 06:00 [medline]
AID - S1097-2765(16)30059-4 [pii]
AID - 10.1016/j.molcel.2016.04.009 [doi]
PST - ppublish
SO  - Mol Cell. 2016 May 5;62(3):359-370. doi: 10.1016/j.molcel.2016.04.009.