DICP OpenIR
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
Source PublicationNATURE
2017-08-03
DOI10.1038/nature23275
Volume548Issue:7665Pages:112-+
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology
WOS SubjectMultidisciplinary Sciences
WOS Research AreaScience & Technology - Other Topics
WOS KeywordVACUOLAR H+-ATPASE ; ACTIVATED PROTEIN-KINASE ; PHOSPHORYLATION ; DISEASE ; CELLS ; METABOLISM ; MECHANISM ; AUTOPHAGY ; REVEALS ; COMPLEX
AbstractThe 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.
Language英语
WOS IDWOS:000406831700047
Citation statistics
Cited Times:85[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/149824
Collection中国科学院大连化学物理研究所
Affiliation1.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
Recommended Citation
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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