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Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK
Zhang, Chen-Song1; Hawley, Simon A.2; Zong, Yue1; Li, Mengqi1; Wang, Zhichao3,4,5; Gray, Alexander2; Ma, Teng1; Cui, Jiwen1; Feng, Jin-Wei1; Zhu, Mingjiang6; Wu, Yu-Qing1; Li, Terytty Yang1; Ye, Zhiyun1; Lin, Shu-Yong1; Yin, Huiyong6; Piao, Hai-Long3; Hardie, D. G. Rahame2; Lin, Sheng-Cai1
刊名NATURE
2017-08-03
DOI10.1038/nature23275
548期:7665页:112-+
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]VACUOLAR H+-ATPASE ; ACTIVATED PROTEIN-KINASE ; PHOSPHORYLATION ; DISEASE ; CELLS ; METABOLISM ; MECHANISM ; AUTOPHAGY ; REVEALS ; COMPLEX
英文摘要The major energy source for most cells is glucose, from which ATP is generated via glycolysis and/or oxidative metabolism. Glucose deprivation activates AMP-activated protein kinase (AMPK)(1), but it is unclear whether this activation occurs solely via changes in AMP or ADP, the classical activators of AMPK(2-5). Here, we describe an AMP/ADP-independent mechanism that triggers AMPK activation by sensing the absence of fructose-1,6-bisphosphate (FBP), with AMPK being progressively activated as extracellular glucose and intracellular FBP decrease. When unoccupied by FBP, aldolases promote the formation of a lysosomal complex containing at least v-ATPase, ragulator, axin, liver kinase B1 (LKB1) and AMPK, which has previously been shown to be required for AMPK activation(6,7). Knockdown of aldolases activates AMPK even in cells with abundant glucose, whereas the catalysis-defective D34S aldolase mutant, which still binds FBP, blocks AMPK activation. Cell-free reconstitution assays show that addition of FBP disrupts the association of axin and LKB1 with v-ATPase and ragulator. Importantly, in some cell types AMP/ATP and ADP/ATP ratios remain unchanged during acute glucose starvation, and intact AMP-binding sites on AMPK are not required for AMPK activation. These results establish that aldolase, as well as being a glycolytic enzyme, is a sensor of glucose availability that regulates AMPK.
语种英语
WOS记录号WOS:000406831700047
引用统计
文献类型期刊论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/149824
专题中国科学院大连化学物理研究所
作者单位1.Xiamen Univ, Sch Life Sci, Innovat Ctr Cell Signaling Network, State Key Lab Cellular Stress Biol, Xiamen 361102, Fujian, Peoples R China
2.Univ Dundee, Div Cell Signalling & Immunol, Coll Life Sci, Dundee DD1 5EH, Scotland
3.Chinese Acad Sci, Dalian Inst Chem Phys, Sci Res Ctr Translat Med, Dalian 116023, Liaoning, Peoples R China
4.Chinese Acad Sci, Dalian Inst Chem Phys, Key Lab Separat Sci Analyt Chem, Dalian 116023, Liaoning, Peoples R China
5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Food Safety Res, Shanghai 200031, Peoples R China
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GB/T 7714
Zhang, Chen-Song,Hawley, Simon A.,Zong, Yue,et al. Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK[J]. NATURE,2017,548(7665):112-+.
APA Zhang, Chen-Song.,Hawley, Simon A..,Zong, Yue.,Li, Mengqi.,Wang, Zhichao.,...&Lin, Sheng-Cai.(2017).Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK.NATURE,548(7665),112-+.
MLA Zhang, Chen-Song,et al."Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK".NATURE 548.7665(2017):112-+.
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