The endoplasmic reticulum (ER) stress potentially activates the unfolded protein response (UPR) and ER-associated protein degradation (ERAD) as quality-control mechanisms. During ERAD process, the ERAD adaptor protein Ubx2 serves as a bridging factor and transports the misfolded proteins from the ER to the cytosol for subsequent ubiquitylation and proteasomal degradation. Cadmium (Cd) is a toxic metal that initiates ER stress and has an impact on lipid homeostasis and this study focuses on the synergistic impact of Cd exposure and ERAD (using ubx2∆ strain). With Cd exposure in ubx2∆ strain, we observed stunted growth and induction of ER stress. The ER stress was confirmed by measuring the expression of UPR marker (Kar2p), and mRNA expression of ER stress-responsive genes (HAC1, IRE1, ERO1, and PDI1), heat shock responsive genes (HSP104 and HSP60), ERAD pathway genes (DOA10, CDC48, HRD1, and YOS9), and proteasome regulators (UBI14, and RPN4). We also observed aberrant membrane morphology with DiOC6 staining, and interrupted mitochondria with mitotracker dye using microscopic analysis. The cell’s inability to relieve stress through adaptive response results in apoptosis and was assessed using acridine orange (AO)–ethidium bromide (EtBr) staining. In ubx2∆ strain, there was reduction in triacylglycerol (TAG) and lipid droplets (LDs), and increase in the phospholipids. The mRNA expression of lipid metabolic genes (LRO1, DGA1, ARE1, ARE2, and OLE1) supported the lipid pattern observed. Collectively, our data suggest that in Saccharomyces cerevisiae, the Cd exposure on ubx2∆ strain induced cellular stress and has an impact on ERAD, UPR, and LD homeostasis.

内质网（ER）应激可能激活未折叠的蛋白应答（UPR）和与ER相关的蛋白降解（ERAD）作为质量控制机制。在ERAD过程中，ERAD衔接蛋白Ubx2作为桥接因子，将错误折叠的蛋白从ER转运至细胞质，以进行随后的泛素化和蛋白酶体降解。镉（Cd）是一种有毒金属，会引发内质网应激，并影响脂质稳态。本研究的重点是镉暴露和ERAD（使用ubx2Δ菌株）的协同作用。通过在ubx2Δ菌株中暴露Cd ，我们观察到生长受阻和内质网应激的诱导。通过测量UPR标记（Kar2p）的表达和ER应激反应基因的mRNA表达来确认ER应激（HAC1，IRE1，ERO1和PDI1），热休克响应基因（HSP104和HSP60），ERAD途径基因（DOA10，CDC48，HRD1和YOS9）以及蛋白酶体调节剂（UBI14和RPN4）。我们还观察到了DiOC6染色的异常膜形态，并使用线粒体示踪剂染料通过显微镜分析中断了线粒体。细胞无法通过适应性反应缓解压力，导致细胞凋亡，并使用idine啶橙（AO）-溴化乙锭（EtBr）染色进行评估。在ubx2∆中菌株中，三酰基甘油（TAG）和脂滴（LDs）减少，磷脂增加。脂质代谢基因（LRO1，DGA1，ARE1，ARE2和OLE1）的mRNA表达支持观察到的脂质模式。总体而言，我们的数据表明，在酿酒酵母中，Cb暴露于ubx2Δ菌株会诱导细胞应激，并影响ERAD，UPR和LD体内稳态。