| In recent years, mass health damage incidents caused by heavy metal pollution happenedfrequently. Heavy metal pollution and its risk to health become one of the key factors that affectsocial harmony and stability. Cadmium is a toxic heavy metal element, it can achieve a certainaccumulation and transfer in each link of the food chain, and also can be directly absorbed throughthe digestive tract and other organs, producing a series of toxic to the organism. With thedevelopment of industry and agriculture, cadmium pollution becomes serious day by day.Bioremediation is highly praised because of its numerous advantages and the key is to get properspecies which are highly resistant to cadmium. It is necessary to study the absorption andinteracellular distribution of cadmium and investigate the detoxification molecular mechanism forcadmium pollution control and environmental restoration. Saccharomyces cerevisiae is the mostsimple eukaryote. Its genetic operation is simple because of the clear genomes and it is easy tocultivate and harvest. Thus it can be used as a very good model organism to study heavy metalresponse mechanism.Many previous works have demonstrated that cadmium can induce biochemical andphysiological changes in yeast Saccharomyces cerevisiae. However, studies on the influence ofcadmium on the ion balance in the cell and the interaction between cadmium and other ions arestill relatively few in number. In the present study, we first measured the contents of some cations,including Zn2+, Fe3+, Cu2+, K+, Mg2+and Ca2+in yeast cells after the treatment of cadmium usingICP-AES. The data showed that the levels of Zn2+and Fe3+were increased, while those of Cu2+and K+were decreased. The subsequent stress response analysis of cadmium and the selected ionsshowed that the cytotoxicity of cadmium could be attributable to the interference of cadmium withthe intracellular cation homeostasis. Additionally, Zn2+, Ca2+, Fe3+, Mg2+and K+can rescue thetoxic effect of cadmium in yeast.Next, by screening the high expression of the essential gene pool of Saccharomycescerevisiae, we found six response genes after cadmium treatment, including OLE1, PRP16,PCL8, MRS6, NOP1and RTP1. Among them, the overexpression of MRS6can enhance the cell resistance to cadmium significantly. The MRS6gene encodes Rab escort protein, forms acomplex with YPT1p (the Ras-like GTPase), and activates the enzyme activity, involved in thevesicles transport between endoplasmic reticulum to golgi apparatus. Overexpression of MRS6changed the distribution of intracellular cadmium, but the mechanism was independent of theGSH1-YCF1vacuole pathway and also independent of the plasma membrane cadmiumtransporter Pca1p pathway. Our results showed that the cadmium tolerance mediated by MRS6relied on the endoplasmic reticulum and golgi apparatus vesicle transport system integrity, andthat protein transport inhibitor BrefeldinA can effectively prevent cadmium efflux mediated byMRS6. In addition, overexpression of MRS6reduced the UPR induced by cadmium andalleviated the endoplasmic reticulum stress, which is the important reason that overexpressionof MRS6is resistant to cadmium.Finally, we investigated the connection between sulfur starvation and mRNA mistranslationto cadmium resistance. Organisms use highly accurate molecular processes to transcript theirgenes, control the mRNA quality and proofread the ribosome to maintain the fidelity of geneticinformation. The phenotypes from low level mRNA mistranslation in eukaryotes was poorlyinvestigated. Here, we found that cadmium treatment can induce mRNA translation error. Theincrease of mRNA mistranslation led to significant resistance phenotype to cadmium, which wasassociated with the sulfur starvation via the Sul1p transporter. Cysteine biosynthesis was requiredin the process. The results provide a novel mechanism mediating the toxicity of cadmium. |
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