期刊
ACS CHEMICAL BIOLOGY
卷 7, 期 12, 页码 2012-2018出版社
AMER CHEMICAL SOC
DOI: 10.1021/cb3004226
关键词
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资金
- Ministry of Health Welfare, Korea [1120300]
- National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology, Korea [2012011362, 20110030635, 2010-0026035]
- Ministry for Health and Wealfare, Republic of Korea [A092006]
- Korea Health Promotion Institute [1120300] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2012R1A2A2A01011362, 2009-0093144, 과C6A2102, 2010-0026035, 과06A1204] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
The roles of sir-2.1 in C. elegans lifespan extension have been subjects of recent public and academic debates. We applied an efficient workflow for in vivo C-13-labeling of C. elegans and C-13-heteronuclear NMR metabolomics to characterizing the metabolic phenotypes of the sir-2.1 mutant. Our method delivered sensitivity 2 orders of magnitude higher than that of the unlabeled approach, enabling 2D and 3D NMR experiments. Multivariate analysis of the NMR data showed distinct metabolic profiles of the mutant, represented by increases in glycolysis, nitrogen catabolism, and initial lipolysis. The metabolomic analysis defined the sir-2.1 mutant metabotype as the decoupling between enhanced catabolic pathways and ATP generation. We also suggest the relationship between the metabotypes, especially the branched chain amino acids, and the roles of sir-2.1 in the worm lifespan. Our results should contribute to solidifying the roles of sir-2.1, and the described workflow can be applied to studying many other proteins in metabolic perspectives.
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