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dc.contributor.authorIrazusta, Verónica Patricia
dc.contributor.authorMoreno Cermeño, Armando J.
dc.contributor.authorCabiscol Català, Elisa
dc.contributor.authorRos Salvador, Joaquim
dc.contributor.authorTamarit Sumalla, Jordi
dc.date.accessioned2016-06-06T10:22:13Z
dc.date.issued2008
dc.identifier.issn0891-5849
dc.identifier.urihttp://hdl.handle.net/10459.1/57158
dc.description.abstractIron 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 main targets of such stress are not known. In yeast cells lacking the frataxin ortholog YFH1, we have identified a set of 14 carbonylated proteins, which include mitochondrial ATP synthase, phosphoglycerate kinase, pyruvate kinase, and molecular chaperones. Interestingly, most of the target proteins are magnesium- and/or nucleotide-binding proteins. This key feature leads us to postulate that when iron accumulates, chelatable iron replaces magnesium at the corresponding metal-binding site, promoting selective damage to these proteins. Consistent with this hypothesis, in vitro experiments performed with pure pyruvate kinase and phosphoglycerate kinase showed that oxidation of these proteins can be prevented by magnesium and increased by the presence of ATP. Also, chelatable iron, which forms complexes with nucleotides, showed a sevenfold increase in Δyfh1 cells. Moreover, lowering chelatable iron in Δyfh1 cells by desferrioxamine prevented enzyme inactivation. As a general conclusion, we propose that magnesium bound to proteins is replaced by chelatable iron when this metal accumulates. This mechanism explains selective protein oxidation and provides clues for better understanding of iron-overloading pathologies.ca_ES
dc.description.sponsorshipThis work is supported by the Friedreich’s Ataxia Research Alliance (Arlington, VA, USA) and Grants BFU2004-00593/BMC and CSD2007-00020 Consolider- Ingenio 2010 from the Ministerio de Educación y Ciencia (Spain). V.I. is the recipient of a Ph.D. fellowship from the Generalitat de Catalunya.ca_ES
dc.language.isoengca_ES
dc.publisherElsevierca_ES
dc.relationMIECI/PN2004-2007/BFU2004-00593/BMC
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1016/j.freeradbiomed.2008.01.014ca_ES
dc.relation.ispartofFree Radical Biology and Medicine, 2008, vol. 44, núm. 9, p. 1712-1723ca_ES
dc.rights(c) Elsevier Inc., 2008ca_ES
dc.subjectIron-overloadca_ES
dc.subjectProtein carbonylationca_ES
dc.subjectMetal-catalyzed oxidationca_ES
dc.subjectFrataxinca_ES
dc.titleMajor targets of iron-induced protein oxidative damage in frataxin-deficient yeasts are magnesium-binding proteinsca_ES
dc.typearticleca_ES
dc.identifier.idgrec011960
dc.type.versionpublishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_ES
dc.identifier.doihttps://doi.org/10.1016/j.freeradbiomed.2008.01.014
dc.date.embargoEndDate2025-01-01


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