Mitochondrial Hsp60, resistance to oxidative stress, and the labile iron pool are closely connected in Saccharomyces cerevisiae.

In the present study, we have analyzed the role of the molecular chaperone Hsp60 in protection of Saccharomyces cerevisiae against oxidative damage. We constructed mutant strains in which the levels of Hsp60 protein, compared with wild-type cells, were four times greater, and the addition of doxycycline gradually reduces them to 20% of wild-type. Under oxidative-stress conditions, the progressive decrease in Hsp60 levels in these mutants resulted in reduced cell viability and an increase in both cell peroxide species and protein carbonyl content. Protection of Fe/S-containing enzymes from oxidative inactivation was found to be dose-dependent with respect to Hsp60 levels. As these enzymes release their iron ions under oxidative-stress conditions, the intracellular labile iron pool, monitored with calcein, was higher in cells with reduced Hsp60 levels. Consistently, the iron chelator deferoxamine protected low Hsp60-expressing cells from both oxidant-induced death and protein oxidation. These results indicate that the role of Hsp60 in oxidative-stress defense is explained by protection of several Fe/S proteins, which prevent the release of iron ions and thereby avert further damage.