Acetylation of Metabolic Enzymes Coordinates Carbon Source Utilization and Metabolic Flux

被引:831
作者
Wang, Qijun [1 ]
Zhang, Yakun [3 ]
Yang, Chen [4 ,5 ]
Xiong, Hui [1 ,3 ]
Lin, Yan [2 ]
Yao, Jun [2 ]
Li, Hong [4 ,5 ]
Xie, Lu [4 ,5 ]
Zhao, Wei [4 ,5 ]
Yao, Yufeng [6 ]
Ning, Zhi-Bin [4 ,5 ]
Zeng, Rong [4 ,5 ]
Xiong, Yue [2 ,7 ,8 ]
Guan, Kun-Liang [2 ,9 ,10 ]
Zhao, Shimin [1 ,2 ]
Zhao, Guo-Ping [1 ,3 ,4 ,5 ,11 ,12 ]
机构
[1] Fudan Univ, Sch Life Sci, Dept Microbiol, State Key Lab Genet Engn, Shanghai 200032, Peoples R China
[2] Fudan Univ, Inst Biomed Sci, Mol Cell Biol Lab, Shanghai 200032, Peoples R China
[3] Chinese Natl Human Genome Ctr Shanghai, MOST Shanghai Lab Dis & Hlth Genom, Shanghai 201203, Peoples R China
[4] Chinese Acad Sci, Bioinformat Ctr, Key Lab Synthet Biol, Shanghai 200032, Peoples R China
[5] Chinese Acad Sci, Lab Syst Biol, Inst Plant Physiol & Ecol, Shanghai Inst Biol Sci, Shanghai 200032, Peoples R China
[6] Shanghai Jiao Tong Univ, Lab Human Bacterial Pathogenesis, Dept Med Microbiol & Parasitol, Inst Med Sci,Sch Med, Shanghai 200025, Peoples R China
[7] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
[8] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA
[9] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA
[10] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA
[11] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Microbiol, Shatin, Hong Kong, Peoples R China
[12] Chinese Univ Hong Kong, Prince Wales Hosp, Li Ka Shing Inst Hlth Sci, Shatin, Hong Kong, Peoples R China
基金
国家高技术研究发展计划(863计划); 中国国家自然科学基金;
关键词
COA SYNTHETASE; PROTEIN; LYSINE; SIR2;
D O I
10.1126/science.1179687
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Lysine acetylation regulates many eukaryotic cellular processes, but its function in prokaryotes is largely unknown. We demonstrated that central metabolism enzymes in Salmonella were acetylated extensively and differentially in response to different carbon sources, concomitantly with changes in cell growth and metabolic flux. The relative activities of key enzymes controlling the direction of glycolysis versus gluconeogenesis and the branching between citrate cycle and glyoxylate bypass were all regulated by acetylation. This modulation is mainly controlled by a pair of lysine acetyltransferase and deacetylase, whose expressions are coordinated with growth status. Reversible acetylation of metabolic enzymes ensure that cells respond environmental changes via promptly sensing cellular energy status and flexibly altering reaction rates or directions. It represents a metabolic regulatory mechanism conserved from bacteria to mammals.
引用
收藏
页码:1004 / 1007
页数:4
相关论文
共 16 条
[1]   Acetylation inactivates the transcriptional repressor BCL6 [J].
Bereshchenko, OR ;
Gu, W ;
Dalla-Favera, R .
NATURE GENETICS, 2002, 32 (04) :606-613
[2]   Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast Sir2 and human SIRT1 [J].
Bitterman, KJ ;
Anderson, RM ;
Cohen, HY ;
Latorre-Esteves, M ;
Sinclair, DA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (47) :45099-45107
[3]   Lysine Acetylation Targets Protein Complexes and Co-Regulates Major Cellular Functions [J].
Choudhary, Chunaram ;
Kumar, Chanchal ;
Gnad, Florian ;
Nielsen, Michael L. ;
Rehman, Michael ;
Walther, Tobias C. ;
Olsen, Jesper V. ;
Mann, Matthias .
SCIENCE, 2009, 325 (5942) :834-840
[4]   Regulation of acetate metabolism by protein phosphorylation in enteric bacteria [J].
Cozzone, AJ .
ANNUAL REVIEW OF MICROBIOLOGY, 1998, 52 :127-164
[5]   Histone acetylation in chromatin structure and transcription [J].
Grunstein, M .
NATURE, 1997, 389 (6649) :349-352
[6]   Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases [J].
Hallows, William C. ;
Lee, Susan ;
Denu, John M. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (27) :10230-10235
[7]   Responses of the central metabolism in Escherichia coli to phosphoglucose isomerase and glucose-6-phosphate dehydrogenase knockouts [J].
Hua, Q ;
Yang, C ;
Baba, T ;
Mori, H ;
Shimizu, K .
JOURNAL OF BACTERIOLOGY, 2003, 185 (24) :7053-7067
[8]   The silencing protein SIR2 and its homologs are MAD-dependent protein deacetylases [J].
Landry, J ;
Sutton, A ;
Tafrov, ST ;
Heller, RC ;
Stebbins, J ;
Pillus, L ;
Sternglanz, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (11) :5807-5811
[9]   Protein Acetylation Microarray Reveals that NuA4 Controls Key Metabolic Target Regulating Gluconeogenesis [J].
Lin, Yu-yi ;
Lu, Jin-ying ;
Zhang, Junmei ;
Walter, Wendy ;
Dang, Weiwei ;
Wan, Jun ;
Tao, Sheng-Ce ;
Qian, Jiang ;
Zhao, Yingming ;
Boeke, Jef D. ;
Berger, Shelley L. ;
Zhu, Heng .
CELL, 2009, 136 (06) :1073-1084
[10]   Identification of the protein acetyltransferase (Pat) enzyme that acetylates acetyl-CoA synthetase in Salmonella enterica [J].
Starai, VJ ;
Escalante-Semerena, JC .
JOURNAL OF MOLECULAR BIOLOGY, 2004, 340 (05) :1005-1012