Yeast frataxin mutants display decreased superoxide dismutase activity crucial to promote protein oxidative damage
Irazusta, Verónica Patricia
Moreno Cermeño, Armando J.
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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 magnesiumbinding 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 Δyfh1 sensitivity to menadione. Finally, a Δsod1 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.
Is part ofFree Radical Biology and Medicine, 2010, vol. 48, núm. 3
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Major targets of iron-induced protein oxidative damage in frataxin-deficient yeasts are magnesium-binding proteins Irazusta, Verónica Patricia; Moreno Cermeño, Armando J.; Cabiscol Català, Elisa; Ros Salvador, Joaquim; Tamarit Sumalla, Jordi (Elsevier, 2008)Iron accumulation has been associated with several pathological conditions such as Friedreich ataxia. This human disorder is caused by decreased expression of frataxin. Iron-overload triggers oxidative stress, but the ...
Frataxin depletion in yeast triggers up-regulation of iron transport systems before affecting iron-sulfur enzyme activities Moreno Cermeño, Armando J.; Obis Monné, Èlia; Bellí i Martínez, Gemma; Cabiscol Català, Elisa; Ros Salvador, Joaquim; Tamarit Sumalla, Jordi (The American Society for Biochemistry and Molecular Biology, 2010)The primary function of frataxin, a mitochondrial protein involved in iron homeostasis, remains controversial. Using a yeast model of conditional expression of the frataxin homologue YFH1, we analyzed the primary effects ...
Moreno Cermeño, Armando J.; Alsina Obiols, David; Cabiscol Català, Elisa; Tamarit Sumalla, Jordi; Ros Salvador, Joaquim (Elsevier, 2013)Frataxin is a mitochondrial protein involved in iron metabolism whose deficiency in humans causes Friedreich ataxia. We performed transcriptomic and proteomic analyses of conditional Yeast Frataxin Homologue (Yfh1) mutants ...