Metabolites modulation in response to environmental change in S. cerevisiae

초록

Cells modulate various metabolic pathways and cellular components in response to environmental change. Nutrients availability is an environmental change that causes alterations in various cellular metabolisms. Nutritional restriction is known to cause many changes in cellular metabolism, gene expression and aging process. The effect of nutrient restriction, especially calorie restriction, on lifespan regulation has been widely explored. However, the mechanisms are still remained to be elucidated. In order to identify metabolites and related genes responding to nutrient restriction, we subjected yeast to a global metabolite profiling approach called metabolomics and genetic analysis. Metabolic profiling of yeast cells grown in normal and nutrient reduced medium was compared. Among many metabolites, that were drastically changed depend on nutrient availability, we selected alanine for further analysis. Cellular alanine level was drastically decreased in the nutrient restricted cells and decreased alanine level was correlated with increased yeast chronological lifespan. Further genetic and molecular biological studies revealed that ALT1 gene, which encodes alanine amino transferase, is important in regulating cellular alanine accumulation and is required for normal lifespan in yeast.