As a potentially toxic heavy metal, Cadmium (Cd) can cause endoplasmic reticulum and oxidative stress, and thus lead to cell death. To explore the mechanisms of Cd toxicity, we investigated the UPRE-lacZ expression, the intracellular reactive oxygen species (ROS) and cell death in the 151 Cd-sensitive mutants of Saccharomyces cerevisiae in response to Cd stress. We identified 101 genes regulating UPRE-lacZ expression were involved in preventing ROS production and/or cell death from increasing to high levels, while mutants for 72 genes caused both elevated ROS production and cell death, indicating the Cd-induced ROS production and cell death are mediated by UPR. Genes involved in cell wall integrity (CWI) pathway, vacuolar protein sorting (VPS) and vacuolar transport, calcium/calcineurin pathway and PHO pathways were all required for the Cd-induced UPR, intracellular ROS and cell death. To conclude, this study highlights the importance of Cd-induced UPR, intracellular ROS levels and cell death that may play crucial roles in Cd-induced toxicity.

中文翻译：

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酿酒酵母镉中毒机理分析

作为一种潜在有毒的重金属，镉 (Cd) 可引起内质网和氧化应激，从而导致细胞死亡。为了探索 Cd 毒性的机制，我们研究了151 种酿酒酵母Cd 敏感突变体响应 Cd 胁迫的 UPRE- lacZ表达、细胞内活性氧 (ROS) 和细胞死亡。我们鉴定了 101 个调控 UPRE- lacZ 的基因表达参与阻止 ROS 产生和/或细胞死亡增加到高水平，而 72 个基因的突变体导致 ROS 产生增加和细胞死亡，表明 Cd 诱导的 ROS 产生和细胞死亡是由 UPR 介导的。参与细胞壁完整性 (CWI) 通路、液泡蛋白分选 (VPS) 和液泡转运、钙/钙调神经磷酸酶通路和 PHO 通路的基因都是 Cd 诱导的 UPR、细胞内 ROS 和细胞死亡所必需的。总之，这项研究强调了 Cd 诱导的 UPR、细胞内 ROS 水平和细胞死亡的重要性，这些可能在 Cd 诱导的毒性中起关键作用。