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AMPK phosphorylation of FNIP1 (S220) controls mitochondrial function and muscle fuel utilization during exercise

文献类型：期刊论文

作者Xiao, Liwei5; Yin, Yujing4,5; Sun, Zongchao4,5; Liu, Jing4,5; Jia, Yuhuan4,5; Yang, Likun4,5; Mao, Yan4,5; Peng, Shujun3,4; Xie, Zhifu2,4; Fang, Lei1,4
刊名SCIENCE ADVANCES
出版日期2024-02-07
卷号10期号:6页码:15
ISSN号2375-2548
DOI10.1126/sciadv.adj2752
通讯作者Xie, Xiaoduo(ganzj@nju.edu.cn) ; Gan, Zhenji(xiexd8@mail.sysu.edu.cn)
英文摘要Exercise-induced activation of adenosine monophosphate-activated protein kinase (AMPK) and substrate phosphorylation modulate the metabolic capacity of mitochondria in skeletal muscle. However, the key effector(s) of AMPK and the regulatory mechanisms remain unclear. Here, we showed that AMPK phosphorylation of the folliculin interacting protein 1 (FNIP1) serine-220 (S220) controls mitochondrial function and muscle fuel utilization during exercise. Loss of FNIP1 in skeletal muscle resulted in increased mitochondrial content and augmented metabolic capacity, leading to enhanced exercise endurance in mice. Using skeletal muscle-specific nonphosphorylatable FNIP1 (S220A) and phosphomimic (S220D) transgenic mouse models as well as biochemical analysis in primary skeletal muscle cells, we demonstrated that exercise-induced FNIP1 (S220) phosphorylation by AMPK in muscle regulates mitochondrial electron transfer chain complex assembly, fuel utilization, and exercise performance without affecting mechanistic target of rapamycin complex 1-transcription factor EB signaling. Therefore, FNIP1 is a multifunctional AMPK effector for mitochondrial adaptation to exercise, implicating a mechanism for exercise tolerance in health and disease.
WOS关键词BODY RADIATION-THERAPY ; REGULATORY T-CELLS ; PANCREATIC-CANCER ; TUMOR ; ADENOCARCINOMA ; IMMUNOTHERAPY ; MANAGEMENT ; BLOCKADE
资助项目Ministry of Science and technology of china[2018YFA0800700] ; Ministry of Science and technology of china[2022YFA0806000] ; National natural Science Foundation of china[91857105] ; National natural Science Foundation of china[31922033] ; National natural Science Foundation of china[31871439] ; Fundamental Research Funds for the central Universities[021414380511] ; Fundamental Research Funds for the central Universities[021414380529] ; Fundamental Research Funds for the central Universities[021414380533] ; Fundamental Research Funds for the central Universities[021414380524] ; Natural Science Foundation of Guangdong[2019A1515011105] ; China Postdoctoral Science Foundation[2023M731633] ; Natural Science Foundation of Jiangsu Province[BK20230146]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:001190871400019
出版者AMER ASSOC ADVANCEMENT SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/310980]  
专题中国科学院上海药物研究所
通讯作者Xie, Xiaoduo; Gan, Zhenji
作者单位1.Nanjing Univ, Jiangsu Key Lab Mol Med & Chem, Med Sch, Nanjing, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China
3.Sun Yat Sen Univ, Sch Med, Shenzhen Campus, Shenzhen, Peoples R China
4.Nanjing Univ, Affiliated Hosp, Med Sch, Nanjing Drum Tower Hosp,Med Sch,Model Anim Res Ctr, Nanjing, Peoples R China
5.Nanjing Univ, Nanjing Drum tower Hosp, State Key Lab Pharmaceut Biotechnol, Nanjing Drum Tower Hosp,Med Sch,Affiliated Hosp, Nanjing, Peoples R China
推荐引用方式
GB/T 7714		 Xiao, Liwei,Yin, Yujing,Sun, Zongchao,et al. AMPK phosphorylation of FNIP1 (S220) controls mitochondrial function and muscle fuel utilization during exercise[J]. SCIENCE ADVANCES,2024,10(6):15.
APA Xiao, Liwei.,Yin, Yujing.,Sun, Zongchao.,Liu, Jing.,Jia, Yuhuan.,...&Gan, Zhenji.(2024).AMPK phosphorylation of FNIP1 (S220) controls mitochondrial function and muscle fuel utilization during exercise.SCIENCE ADVANCES,10(6),15.
MLA Xiao, Liwei,et al."AMPK phosphorylation of FNIP1 (S220) controls mitochondrial function and muscle fuel utilization during exercise".SCIENCE ADVANCES 10.6(2024):15.

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来源：上海药物研究所

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