Abstract: Iron overload is involved in several pathological conditions, including Friedreich ataxia, a disease caused by decreased expression of the mitochondrial protein frataxin. In a previous study,we identified 14 proteins selectively oxidized in yeast cells lacking Yfh1, the yeast frataxin homolog. Most of these were magnesium-binding proteins. Decreased Mn-SOD activity, oxidative damage to CuZn-SOD, and increased levels of chelatable iron were also observed in this model. The present study explores the relationship between low SOD activity, the presence of chelatable iron and protein damage was investigated in more detail. We observed that addition of copper and manganese to the culture medium restored SOD activities prevented both oxidative damage and inactivation of magnesium-binding proteins. This protection was compartment-specific: recovery of mitochondrial enzymes required the addition of manganese while cytosolic enzymes were recovered by adding copper. Copper treatment also decreased Deltayfh1 sensitivity to menadione. Finally, a Deltasod1 mutant showed high levels of chelatable iron and inactivation of magnesium-binding enzymes. These results suggest that reduced superoxide dismutase activities contribute to the toxic effects of iron overloading. This would also apply to pathologies involving iron accumulation.