Alanine-Metabolizing Enzyme Alt1 Is Critical in Determining Yeast Life Span, As Revealed by Combined Metabolomic and Genetic Studies

Title
Alanine-Metabolizing Enzyme Alt1 Is Critical in Determining Yeast Life Span, As Revealed by Combined Metabolomic and Genetic Studies
Authors
이성근
Keywords
life span, alanine, ALT1, metabolomics, NMR, yeast
Issue Date
2013
Publisher
JOURNAL OF PROTEOME RESEARCH
Series/Report no.
JOURNAL OF PROTEOME RESEARCH ; Vol.12 no.4 Startpage 1619 Endpage 1627
Abstract
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 alaninemetabolizing 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.
URI
http://dspace.inha.ac.kr/handle/10505/31512
ISSN
1535-3893
Appears in Collections:
Medical School/College of Medicine (의학전문대학원/의과대학) > Medical Science (의학) > Journal Papers, Reports(의학 논문, 보고서)

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