Saccharomyces cerevisiae MED2/YDL005C is a subunit of the mediator complex (Mediator), which is responsible for tightly controlling the transcription of protein-coding genes by mediating the interaction of RNA polymerase II with gene-specific transcription factors. Although a high-throughput analysis in yeast showed that the MED2 protein exhibits altered cellular localization under hypoxic stress, no specific function of MED2 has been described to date. In this study, we first provided evidence that MED2 is involved in the endoplasmic reticulum (ER) stress response and modulation of the replicative life span. We showed that deletion of MED2 leads to sensitivity to the ER stress inducer tunicamycin (TM) as well as a shortened replicative lifespan (RLS), accompanied by increased intracellular ROS levels and hyperpolarization of mitochondria. On the other hand, overexpression of MED2 in wild-type (WT) yeast enhanced TM resistance and extended the RLS. In addition, the IRE1-HAC1 pathway was essential for the TM resistance of MED2-overexpressing cells. Moreover, we showed that MED2 deficiency enhances ER unfolded protein response (UPR) activity compared to that in WT cells. Collectively, these results suggest the novel role of MED2 as a regulator in maintaining ER homeostasis and longevity.

Saccharomyces cerevisiae MED2 /YDL005C是介体复合物（Mediator）的一个亚基，它负责通过介导RNA聚合酶II与基因特异性转录因子的相互作用来严密控制蛋白质编码基因的转录。尽管酵母中的高通量分析表明MED2蛋白在缺氧应激下表现出改变的细胞定位，但迄今为止尚未描述MED2 的特定功能。在这项研究中，我们首先提供了MED2参与内质网 (ER) 应激反应和复制寿命调节的证据。我们发现MED2 的缺失导致对内质网应激诱导剂衣霉素 (TM) 的敏感性以及复制寿命 (RLS) 的缩短，伴随着细胞内 ROS 水平的增加和线粒体的超极化。另一方面，MED2在野生型 (WT) 酵母中的过表达增强了 TM 抗性并延长了 RLS。此外，IRE1 - HAC1通路对于MED2过表达细胞的 TM 抗性是必不可少的。此外，我们发现与 WT 细胞相比，MED2缺乏增强了 ER 未折叠蛋白反应（UPR）活性。总的来说，这些结果表明MED2作为调节剂在维持 ER 稳态和寿命方面的新作用。