Glutaredoxin Deletion Shortens Chronological Life Span in <i>Saccharomyces cerevisiae</i> via ROS-Mediated Ras/PKA Activation

Glutaredoxins (GRXs),
small redox proteins that use reduced glutathione
as an electron donor, are key components of the cellular antioxidant
system. In this study, we used Saccharomyces cerevisiae as a model system to investigate the effects of GRX deletion on
yeast chronological life span (CLS). Deletion of either Grx1 or Grx2
shortened yeast CLS. Quantitative proteomics revealed that GRX deletion
decreased the expression of stress-response proteins, leading to increased
cellular reactive oxygen species accumulation and, subsequently, intracellular
acidification. This activated the Ras/protein kinase A (PKA) signaling
pathway. Genetic and biochemical analyses demonstrated that Ras/PKA
activation decreased stress resistance and increased biosynthesis,
requiring yeast cells to grow under unfavorable conditions and resulting
in a shortened CLS. Our results provided new insights into mechanisms
underlying exacerbation of the aging process by oxidative stress.