Hierarchical activation of compartmentalized pools of AMPK depends on severity of nutrient or energy stress

doi:10.1038/s41422-019-0163-6

	Hierarchical activation of compartmentalized pools of AMPK depends on severity of nutrient or energy stress
	Zong, Yue 4; Zhang, Chen-Song 4; Li, Mengqi 4; Wang, Wen 2,3; Wang, Zhichao 2,3; Hawley, Simon A.1; Ma, Teng 4; Feng, Jin-Wei 4; Tian, Xiao 4; Qi, Qu 4
刊名	CELL RESEARCH
	2019-06-01
卷号	29 期号:6 页码:460-473
ISSN号	1001-0602
DOI	10.1038/s41422-019-0163-6
通讯作者	Lin, Sheng-Cai(linsc@xmu.edu.cn)
英文摘要	AMPK, a master regulator of metabolic homeostasis, is activated by both AMP-dependent and AMP-independent mechanisms. The conditions under which these different mechanisms operate, and their biological implications are unclear. Here, we show that, depending on the degree of elevation of cellular AMP, distinct compartmentalized pools of AMPK are activated, phosphorylating different sets of targets. Low glucose activates AMPK exclusively through the AMP-independent, AXIN-based pathway in lysosomes to phosphorylate targets such as ACC1 and SREBP1c, exerting early anti-anabolic and pro-catabolic roles. Moderate increases in AMP expand this to activate cytosolic AMPK also in an AXIN-dependent manner. In contrast, high concentrations of AMP, arising from severe nutrient stress, activate all pools of AMPK independently of AXIN. Surprisingly, mitochondrion-localized AMPK is activated to phosphorylate ACC2 and mitochondrial fission factor (MFF) only during severe nutrient stress. Our findings reveal a spatiotemporal basis for hierarchical activation of different pools of AMPK during differing degrees of stress severity.
资助项目	National Key R&D Program of China[2016YFA0502001] ; National Natural Science Foundation of China[31730058] ; National Natural Science Foundation of China[31430094] ; National Natural Science Foundation of China[31601152] ; National Natural Science Foundation of China[31690101] ; Open Research Fund of State Key Laboratory of Cellular Stress Biology, Xiamen University[SKLCSB2017KF002] ; Wellcome Trust[204766/Z/16/Z]
WOS关键词	ACETYL-COA CARBOXYLASE ; PROTEIN-KINASE ; SUBCELLULAR-LOCALIZATION ; DIFFERENTIAL REGULATION ; MITOCHONDRIAL FISSION ; HEPATIC STEATOSIS ; INDUCED AUTOPHAGY ; STRUCTURAL BASIS ; RAG GTPASES ; PHOSPHORYLATION
WOS研究方向	Cell Biology
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000470082200007
资助机构	National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Open Research Fund of State Key Laboratory of Cellular Stress Biology, Xiamen University ; Open Research Fund of State Key Laboratory of Cellular Stress Biology, Xiamen University ; Wellcome Trust ; Wellcome Trust ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Open Research Fund of State Key Laboratory of Cellular Stress Biology, Xiamen University ; Open Research Fund of State Key Laboratory of Cellular Stress Biology, Xiamen University ; Wellcome Trust ; Wellcome Trust ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Open Research Fund of State Key Laboratory of Cellular Stress Biology, Xiamen University ; Open Research Fund of State Key Laboratory of Cellular Stress Biology, Xiamen University ; Wellcome Trust ; Wellcome Trust ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Open Research Fund of State Key Laboratory of Cellular Stress Biology, Xiamen University ; Open Research Fund of State Key Laboratory of Cellular Stress Biology, Xiamen University ; Wellcome Trust ; Wellcome Trust
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/172143]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Lin, Sheng-Cai
作者单位	1.Univ Dundee, Coll Life Sci, Div Cell Signalling & Immunol, Dundee DD1 5EH, Scotland 2.Chinese Acad Sci, Dalian Inst Chem Phys, CAS Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361102, Fujian, Peoples R China
推荐引用方式 GB/T 7714	Zong, Yue,Zhang, Chen-Song,Li, Mengqi,et al. Hierarchical activation of compartmentalized pools of AMPK depends on severity of nutrient or energy stress[J]. CELL RESEARCH,2019,29(6):460-473.
APA	Zong, Yue.,Zhang, Chen-Song.,Li, Mengqi.,Wang, Wen.,Wang, Zhichao.,...&Lin, Sheng-Cai.(2019).Hierarchical activation of compartmentalized pools of AMPK depends on severity of nutrient or energy stress.CELL RESEARCH,29(6),460-473.
MLA	Zong, Yue,et al."Hierarchical activation of compartmentalized pools of AMPK depends on severity of nutrient or energy stress".CELL RESEARCH 29.6(2019):460-473.