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Título:
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Yeast frataxin mutants display decreased superoxide dismutase activity crucial to promote protein oxidative damage
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Autor/a:
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Irazusta, Verónica Patricia; Obis Monné, Èlia; Moreno Cermeño, Armando J.; Cabiscol Català, Elisa; Ros Salvador, Joaquim; Tamarit Sumalla, Jordi
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Notas:
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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.
This work was supported by Grants BFU2004-00593/BMC and CSD2007-00020 from the Ministerio de Ciencia e Innovacion and SGR 0677 from Generalitat de Catalunya (Spain). V.I. received a Ph.D. fellowship from the Generalitat de Catalunya. We thank Elaine M. Lilly for editorial assistance. |
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Materia(s):
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-Iron overload
-Protein carbonylation
-Metal-catalyzed oxidation |
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Derechos:
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(c) Elsevier, 2010
info:eu-repo/semantics/restrictedAccess |
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Tipo de documento:
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article
publishedVersion |
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Editor:
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Elsevier
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Compartir:
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