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.

中文翻译：

---

Glutaredoxin删除通过ROS介导的Ras / PKA激活缩短酿酒酵母的时间寿命。

谷胱甘肽毒素（GRXs）是使用还原型谷胱甘肽作为电子供体的小型氧化还原蛋白，是细胞抗氧化剂系统的关键成分。在这项研究中，我们使用了酿酒酵母作为研究GRX缺失对酵母按时间顺序（CLS）的影响的模型系统。删除Grx1或Grx2缩短的酵母CLS。定量蛋白质组学表明，GRX缺失降低了应激反应蛋白的表达，从而导致细胞中活性氧的积累增加，进而引起细胞内酸化。这激活了Ras /蛋白激酶A（PKA）信号传导途径。遗传和生化分析表明，Ras / PKA激活降低了抗逆性并增加了生物合成，需要酵母细胞在不利条件下生长并导致CLS缩短。我们的结果提供了新的见解，揭示了氧化应激加剧衰老过程的潜在机制。