Role of glutathione in detoxification of copper and cadmium by yeast cells having different abilities to express cup1 protein.

ABSTRACT Although copper is an essential metal and cadmium is an environmental pollutant, both are toxic when present in excess. Metallothionein and glutathione are two of the key components that participate in detoxification of copper and cadmium. In the present study the role of glutathione in resistance to copper and cadmium was investigated with the yeast Saccharomyces cerevisiae. The yeast cells used in this study have different abilities to produce glutathione and Cup1 protein, the yeast metallothionein homolog encoded by CUP1 gene. It was demonstrated that Cup1 protein plays a dominant role in buffering excess copper, and yeast does not depend on glutathione to reduce copper toxicity whether it possesses single or multiple copies of CUP1. In fact, excess copper can cause glutathione oxidation and depletion and damage the glutathione system. On the other hand, it was indicated that Cup1 protein is an important cadmium-detoxifying component, and the glutathione system can positively respond to cadmium. In yeast containing single or multiple copies of CUP1, glutathione is an indispensable line of defense against cadmium. Yeast having glutathione and no Cup1 protein is not able to grow in medium containing excess copper, but can tolerate higher concentrations of cadmium. In addition, it was found that yeast, independent of glutathione, can efficiently remove excess copper, whereas it cannot promptly eliminate accumulated cadmium regardless of having glutathione or not.