西亚试剂：Regulation of Cellular Metabolism by Protein Lysine Acetyla

发布时间：2025-10-24

Regulation of Cellular Metabolism by Protein Lysine Acetylation
Shimin Zhao,1,2 Wei Xu,1,2,* Wenqing Jiang,1,2,* Wei Yu,1,2 Yan Lin,2 Tengfei Zhang,1,2 Jun Yao,3 Li Zhou,4 Yaxue Zeng,4 Hong Li,5 Yixue Li,6 Jiong Shi,6 Wenlin An,7 Susan M. Hancock,7 Fuchu He,3 Lunxiu Qin,5 Jason Chin,7 Pengyuan Yang,3 Xian Chen,3,4 Qunying Lei,1,2,8 Yue Xiong,1,2,4, Kun-Liang Guan1,2,8,9,

Protein lysine acetylation has emerged as a key posttranslational modification in cellular regulation, in particular through the modification of histones and nuclear transcription regulators. We show that lysine acetylation is a prevalent modification in enzymes that catalyze intermediate metabolism. Virtually every enzyme in glycolysis, gluconeogenesis, the tricarboxylic acid (TCA) cycle, the urea cycle, fatty acid metabolism, and glycogen metabolism was found to be acetylated in human liver tissue. The concentration of metabolic fuels, such as glucose, amino acids, and fatty acids, influenced the acetylation status of metabolic enzymes. Acetylation activated enoyl–coenzyme A hydratase/3-hydroxyacyl–coenzyme A dehydrogenase in fatty acid oxidation and malate dehydrogenase in the TCA cycle, inhibited argininosuccinate lyase in the urea cycle, and destabilized phosphoenolpyruvate carboxykinase in gluconeogenesis. Our study reveals that acetylation plays a major role in metabolic regulation.

1 School of Life Sciences, Fudan University, Shanghai 20032, China.
2 Molecular and Cell Biology Lab, Fudan University, Shanghai 20032, China.
3 Center of Proteomics, Institute of Biomedical Sciences, Fudan University, Shanghai 20032, China.
4 Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
5 Affiliated Zhongshan Hospital, Fudan University, Shanghai 20032, China.
6 Bioinformatics Center, Key Lab of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
7 Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 OQH, UK.
8 Department of Biological Chemistry, Fudan University, Shanghai 20032, China.
9 Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.

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