Alanine-Metabolizing Enzyme Alt1 Is Critical in Determining Yeast Life Span, As Revealed by Combined Metabolomic and Genetic Studies
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- 作者：Sung-Lim Yu ; Yong Jin An ; Hey-ji Yang ; Mi-Sun Kang ; Ho-Yeol Kim ; He Wen ; Xing Jin ; Hyuk Nam Kwon ; Kyung-Jin Min ; Sung-Keun Lee ; Sunghyouk Park
- 刊名：Journal of Proteome Research
- 出版年：2013
- 出版时间：April 5, 2013
- 年：2013
- 卷：12
- 期：4
- 页码：1619-1627
- 全文大小：413K
- 年卷期：v.12,no.4(April 5, 2013)
- ISSN：1535-3907
文摘
Alterations in metabolic pathways are gaining attention as important environmental factors affecting life span, but the determination of specific metabolic pathways and enzymes involved in life span remains largely unexplored. By applying an NMR-based metabolomics approach to a calorie-restricted yeast (Saccharomyces cerevisiae) model, we found that alanine level is inversely correlated with yeast chronological life span. The involvement of the alanine-metabolizing pathway in the life span was tested using a deletion mutant of ALT1, the gene for a key alanine-metabolizing enzyme. The mutant exhibited increased endogenous alanine level and much shorter life span, demonstrating the importance of ALT1 and alanine metabolic pathways in the life span. ALT1鈥檚 effect on life span was independent of the TOR pathway, as revealed by a tor1 deletion mutant. Further mechanistic studies showed that alt1 deletion suppresses cytochrome c oxidase subunit 2 expression, ultimately generating reactive oxygen species. Overall, ALT1 seems critical in determining yeast life span, and our approach should be useful for the mechanistic studies of life span determinations.