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dc.contributor.authorAlsina Obiols, David
dc.contributor.authorRos Salvador, Joaquim
dc.contributor.authorTamarit Sumalla, Jordi
dc.description.abstractYeast frataxin homolog (Yfh1) is the orthologue of human frataxin, a mitochondrial protein whose deficiency causes Friedreich Ataxia. Yfh1 deficiency activates Aft1, a transcription factor governing iron homeostasis in yeast cells. Although the mechanisms causing this activation are not completely understood, it is assumed that it may be caused by iron-sulfur deficiency. However, several evidences indicate that activation of Aft1 occurs in the absence of iron-sulfur deficiency. Besides, Yfh1 deficiency also leads to metabolic remodeling (mainly consisting in a shift from respiratory to fermentative metabolism) and to induction of Yhb1, a nitric oxide (NO) detoxifying enzyme. In this work, we have used conditional Yfh1 mutant yeast strains to investigate the relationship between NO, Aft1 activation and metabolic remodeling. We have observed that NO prevents Aft1 activation caused by Yfh1 deficiency. This phenomenon is not observed when Aft1 is activated by iron scarcity or impaired iron-sulfur biogenesis. In addition, analyzing key metabolic proteins by a targeted proteomics approach, we have observed that NO prevents the metabolic remodeling caused by Yfh1 deficiency. We conclude that Aft1 activation in Yfh1-deficient yeasts is not caused by iron-sulfur deficiency or iron scarcity. Our hypothesis is that Yfh1 deficiency leads to the presence of anomalous iron species that can compromise iron bioavailability and activate a signaling cascade that results in Aft1 activation and metabolic remodeling.ca_ES
dc.description.sponsorshipThis work was supported by grants SAF2013-44820-R to J.R. (from Ministerio de Economia y Competitividad (Spain) and SGR2009-00196 from the Generalitat de Catalunya). We thank Roser Pané for technical assistance.ca_ES
dc.relation.isformatofReproducció del document publicat a
dc.relation.ispartofRedox Biology, 2018, vol. 14, p. 131-141ca_ES
dc.rightscc-by-nc-nd, (c) David Alsina et al., 2017ca_ES
dc.subjectFriedreich ataxiaca_ES
dc.subjectNitric oxideca_ES
dc.subjectTargeted proteomicsca_ES
dc.titleNitric oxide prevents Aft1 activation and metabolic remodeling in frataxindeficient yeastca_ES

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cc-by-nc-nd, (c) David Alsina et al., 2017
Except where otherwise noted, this item's license is described as cc-by-nc-nd, (c) David Alsina et al., 2017