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dc.contributor.authorMoreno Cermeño, Armando J.
dc.contributor.authorAlsina Obiols, David
dc.contributor.authorCabiscol Català, Elisa
dc.contributor.authorTamarit Sumalla, Jordi
dc.contributor.authorRos Salvador, Joaquim
dc.date.accessioned2016-05-10T09:58:00Z
dc.date.issued2013
dc.identifier.issn0006-3002
dc.identifier.urihttp://hdl.handle.net/10459.1/57012
dc.description.abstractFrataxin 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 (tetO7-YFH1) to investigate metabolic remodeling upon Yfh1 depletion. These studies revealed that Yfh1 depletion leads to downregulation of many glucose-repressed genes. Most of them were Adr1 targets, a key transcription factor required for growth in non-fermentable carbon sources. Using a GFP-tagged Adr1, we observed that Yfh1 depletion promotes the export of Adr1 from the nucleus to the cytosol without affecting its protein levels. This effect was also observed upon H2O2 treatment, but not by iron overload/starvation, indicating the presence of a regulatory pathway involved in Adr1 export and inactivation upon stress conditions. We also observed that CTH2, a gene involved in the mRNA degradation of several iron-containing enzymes, was induced upon Yfh1 depletion. Accordingly, decreased levels of aconitase and succinate dehydrogenase were observed. Nevertheless, their levels were maintained in a Δcth2 mutant even in the absence of Yfh1. From these results we can conclude that, in addition to altering iron homeostasis, frataxin depletion involves drastic metabolic remodeling governed by Adr1 and Cth2 that finally leads to downregulation of iron–sulfur proteins and other proteins involved in respiratory metabolism.ca_ES
dc.description.sponsorshipThis work was supported by grants to J.R. BFU2010-19193, and CSD2007-00020 Consolider Ingenio 2010 fromMinisterio de Economia y Competitividad (Spain), SGR2009-00196 from the Generalitat de Catalunya and to J.T. from La Marató de TV3 2010.ca_ES
dc.language.isoengca_ES
dc.publisherElsevierca_ES
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1016/j.bbamcr.2013.09.019ca_ES
dc.relation.ispartofBiochimica et Biophysica Acta, 2013, vol. 1833, núm. 12, p. 3326-3337ca_ES
dc.rights(c) Elsevier, 2013ca_ES
dc.subjectFriedreich ataxiaca_ES
dc.subjectYeast frataxinca_ES
dc.subjectIronca_ES
dc.titleMetabolic remodeling in frataxin-deficient yeast is mediated by Cth2 and Adr1ca_ES
dc.typearticleca_ES
dc.identifier.idgrec021768
dc.type.versionpublishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_ES
dc.identifier.doihttps://doi.org/10.1016/j.bbamcr.2013.09.019
dc.date.embargoEndDate2025-01-01


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