Metabolic remodeling in frataxin-deficient yeast is mediated by Cth2 and Adr1
Moreno Cermeño, Armando J.
Alsina Obiols, David
MetadataShow full item record
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 (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.
Is part ofBiochimica et Biophysica Acta, 2013, vol. 1833, núm. 12, p. 3326-3337
European research projects
Showing items related by title, author, creator and subject.
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 ...
Alsina Obiols, David; Ros Salvador, Joaquim; Tamarit Sumalla, Jordi (Elsevier, 2018)Yeast 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 ...
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 ...