Glutaredoxin Deletion Shortens Chronological Life Span In Saccharomyces Cerevisiae

In the present days,the problem of population aging is becoming more and more obvious.ROS is tightly connected to aging progress and aging-related diseases.As organisms grow older,ROS gradually accumulate,leading to cell damage and aging-related diseases.Glutaredoxins play important roles in cellular antioxidant system and use GSH as electron donor to catalyze reduction of protein disulfide bonds or low-molecular weight disulphide.Budding yeast(Saccharomyces cerevisiae)is one of the most important model organisms for aging-related researches.It has two classical dithiol glutaredoxins: Grx1,which is located in cytoplasm and Grx2,which is located in cytoplasm and mitochondria.Previous studies showed that both expression level and activity of Grx1 decreased with aging in mice and mitochondrial Grxs play essential roles in aging.In the present study,we investigated the relationship between Grx deletion and yeast chronological life span(CLS).We found that Grx-deletion shortened yeast CLS.Then we used quantitative proteomic analysis to identify differentially expressed proteins between Grx-deleted yeast and wildtype yeast,and found that Ras-PKA pathway was activated in Grx-deleted yeast.We further verified the activation of Ras-PKA pathway in Grx-deleted yeast by examining related phenotypes.We also decreased Ras-PKA activity in Grx-deleted yeast by overexpressing Ras-PKA repression proteins and found that the CLS of Grx-deleted yeast increased.Finally,we found that Grx deletion increased cellular ROS which led to decreased cellular p H and Ras-PKA activation in yeast.Taken together,by using quantitative proteomic analysis and phenotype experiments,our studies showed that Grx deletion increased cellular ROS level and activated Ras-PKA pathway,leading to decreased stress adaptive responses and increased biosynthesis,which accelerated the aging process.Our results provided new insight for aging-related researches.