Cytotoxic and genotoxic consequences of heat stress are dependent on the presence of oxygen in Saccharomyces cerevisiae

Lethal heat stress generates oxidative stress in Saccharomyces cerevisiae, and anaerobic cells are several orders of magnitude more resistant than aer obic cells to a 50 degreesC heat shock, Here we characterize the oxidative effects of this heat stress. The thermoprotective effect in anaerobic cells was not due to expression of HSP104 or any other heat shock gene, raising the possibility that the toxicity of lethal heat shock is due mainly to oxi dative stress. Aerobic but not anaerobic heat stress caused elevated freque ncies of forward mutations and interchromosomal DNA recombination, Oxidativ e DNA repair glycosylase-deficient strains under aerobic conditions showed a powerful induction of forward mutation frequencies compared to wild-type cells, which was completely abolished under anaerobiosis, We also investiga ted potential causes for this oxygen-dependent heat shock-induced genetic i nstability. Levels of sulfhydryl groups, dominated mainly by the high level s of the antioxidant glutathione (reduced form) and levels of vitamin E, de creased after aerobic heat stress but not after anaerobic heat stress. Aero bic heat stress also led to an increase in mitochondrial membrane disruptio n of several hundredfold, which was 100-fold reduced under anaerobic condit ions.