Calcium signaling and copper toxicity in Saccharomyces cerevisiae cells

To respond to metal surpluses, cells have developed intricate ways of defense against the excessive metallic ions. To understand the ways in which cells sense the presence of toxic concentration in the environment, the role of Ca²⁺ in mediating the cell response to high Cu²⁺ was investigated in Saccharomyces cerevisiae cells. It was found that the cell exposure to high Cu²⁺ was accompanied by elevations in cytosolic Ca²⁺ with patterns that were influenced not only by Cu²⁺ concentration but also by the oxidative state of the cell. When Ca²⁺ channel deletion mutants were used, it was revealed that the main contributor to the cytosolic Ca²⁺ pool under Cu²⁺ stress was the vacuolar Ca²⁺ channel, Yvc1, also activated by the Cch1-mediated Ca²⁺ influx. Using yeast mutants defective in the Cu²⁺ transport across the plasma membrane, it was found that the Cu²⁺-dependent Ca²⁺ elevation could correlate not only with the accumulated metal, but also with the overall oxidative status. Moreover, it was revealed that Cu²⁺ and H₂O₂ acted in synergy to induce Ca²⁺-mediated responses to external stress.