Exogenous oxidative stress induces Ca2+release in the yeast Saccharomyces cerevisiae

The Ca2+-dependent response to oxidative stress caused by H2O2 or tert-butylhydroperoxide (tBOOH) was investigated in Saccharomyces cerevisiae cells expressing transgenic cytosolic aequorin, a Ca2+-dependent photoprotein. Both H2O2 and tBOOH induced an immediate and short-duration cytosolic Ca2+ increase that depended on the concentration of the stressors. Sublethal doses of H2O2 induced Ca2+ entry into the cytosol from both extracellular and vacuolar sources, whereas lethal H2O2 shock mobilized predominantly the vacuolar Ca2+. Sublethal and lethal tBOOH shocks induced mainly the influx of external Ca2+, accompanied by a more modest vacuolar contribution. Ca2+ transport across the plasma membrane did not necessarily involve the activity of the Cch1p/Mid1p channel, whereas the release of vacuolar Ca2+ into the cytosol required the vacuolar channel Yvc1p. In mutants lacking the Ca2+ transporters, H2O2 or tBOOH sensitivity correlated with cytosolic Ca2+ overload. Thus, it appears that under H2O2-induced or tBOOH-induced oxidative stress, Ca2+ mediates the cytotoxic effect of the stressors and not the adaptation process.