title: Alanine-metabolizing enzyme Alt1 is critical in determining yeast life span, as revealed by combined metabolomic and genetic studies.
abstract: 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's 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.
authors.affiliation: Inha Research Institute for Medical Sciences, ‡Department of Biochemistry, and §Department of Pharmacology, Center for Advanced Medical Education by BK21 project, College of Medicine and ∥Department of Biological Sciences, Inha University , Incheon, Korea, 400-712.
authors.forename: Sung-Lim
authors.initials: SL
authors.lastname: Yu
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: An
authors.forename: Hey-Ji
authors.initials: HJ
authors.lastname: Yang
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Kang
authors.forename: Ho-Yeol
authors.initials: HY
authors.lastname: Kim
authors.forename: He
authors.initials: H
authors.lastname: Wen
authors.forename: Xing
authors.initials: X
authors.lastname: Jin
authors.forename: Hyuk Nam
authors.initials: HN
authors.lastname: Kwon
authors.forename: Kyung-Jin
authors.initials: KJ
authors.lastname: Min
authors.forename: Sung-Keun
authors.initials: SK
authors.lastname: Lee
authors.forename: Sunghyouk
authors.initials: S
authors.lastname: Park
mesh_terms: D000410:Alanine Transaminase / Q000235:genetics / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D017353:Gene Deletion; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics / Q000379:methods; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000410:Alanine Transaminase; D003576:Electron Transport Complex IV; D019869:Phosphatidylinositol 3-Kinases; D029701:Saccharomyces cerevisiae Proteins; C083324:TOR1 protein, S cerevisiae