Hierarchical activation of compartmentalized pools of AMPK depends on severity of nutrient or energy stress
文献类型：期刊论文
| 作者 | Zong, Yue4; Zhang, Chen-Song4; Li, Mengqi4; Wang, Wen2,3; Wang, Zhichao2,3; Hawley, Simon A.1; Ma, Teng4; Feng, Jin-Wei4; Tian, Xiao4; Qi, Qu4 |
| 刊名 | CELL RESEARCH
 |
| 出版日期 | 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. |
| WOS关键词 | ACETYL-COA CARBOXYLASE ; PROTEIN-KINASE ; SUBCELLULAR-LOCALIZATION ; DIFFERENTIAL REGULATION ; MITOCHONDRIAL FISSION ; HEPATIC STEATOSIS ; INDUCED AUTOPHAGY ; STRUCTURAL BASIS ; RAG GTPASES ; PHOSPHORYLATION |
| 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 |
| 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. |
入库方式： OAI收割
来源：大连化学物理研究所
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