title: Yeast frataxin mutants display decreased superoxide dismutase activity crucial to promote protein oxidative damage.
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. This study explores the relationship between low SOD activity, the presence of chelatable iron, and protein damage. We observed that addition of copper and manganese to the culture medium restored SOD activity and prevented both oxidative damage and inactivation of magnesium-binding proteins. This protection was compartment specific: recovery of mitochondrial enzymes required the addition of manganese, whereas 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 activity contributes to the toxic effects of iron overloading. This would also apply to pathologies involving iron accumulation.
authors.affiliation: Grup de Bioquímica de l'Estrés Oxidatiu, Departament de Ciències Mèdiques Bàsiques, Facultat de Medicina, Universitat de Lleida, 25008 Lleida, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Irazusta
authors.forename: Elia
authors.initials: E
authors.lastname: Obis
authors.forename: Armando
authors.initials: A
authors.lastname: Moreno-Cermeño
authors.forename: Elisa
authors.initials: E
authors.lastname: Cabiscol
authors.forename: Joaquim
authors.initials: J
authors.lastname: Ros
authors.forename: Jordi
authors.initials: J
authors.lastname: Tamarit
mesh_terms: D003300:Copper / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D015966:Gene Expression Regulation, Fungal; D007501:Iron / Q000378:metabolism; D033862:Iron-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011506:Proteins / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*; D000096923:Frataxin
chemical_list: D003300:Copper; D007501:Iron; D033862:Iron-Binding Proteins; D008345:Manganese; D011506:Proteins; D013482:Superoxide Dismutase; D000096923:Frataxin