title: Cells lacking pfh1, a fission yeast homolog of mammalian frataxin protein, display constitutive activation of the iron starvation response.
abstract: Friedreich ataxia is a genetic disease caused by deficiencies in frataxin. This protein has homologs not only in higher eukaryotes but also in bacteria, fungi, and plants. The function of this protein is still controversial. We have identified a frataxin homolog in fission yeast, and we have analyzed whether its depletion leads to any of the phenotypes observed in other organisms. Cells deleted in pfh1 are sensitive to growth under aerobic conditions, display increased levels of total iron, hallmarks of oxidative stress such as protein carbonylation, decreased aconitase activity, and lower levels of oxygen consumption compared with wild-type cells. This mitochondrial protein seems to be important for iron and/or reactive oxygen species homeostasis. We have analyzed the proteome of cells devoid of Pfh1, and we determined that gene products up- and down-regulated upon iron depletion in wild-type cells are constitutively misregulated in this mutant. Because of the particular signaling pathway components governing the iron starvation response in fission yeast, our experiments suggest that cells lacking Pfh1 display a decrease of cytosolic available iron that triggers activation of Grx4, the common regulator of the iron starvation gene expression program. Our Schizosaccharomyces pombe Δpfh1 strain constitutes a new and useful model system to study Friedreich ataxia.
authors.affiliation: Oxidative Stress and Cell Cycle Group, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, C/Dr. Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Gabrielli
authors.forename: José
authors.initials: J
authors.lastname: Ayté
authors.forename: Elena
authors.initials: E
authors.lastname: Hidalgo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004265:DNA Helicases / Q000737:chemistry / Q000172:deficiency* / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal / Q000235:genetics; D006801:Humans; D000090463:Iron Deficiencies; D033862:Iron-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D008322:Mammals / Q000378:metabolism*; D008969:Molecular Sequence Data; D010641:Phenotype; D020543:Proteome / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D059467:Transcriptome / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D000096923:Frataxin
chemical_list: D004265:DNA Helicases; D033862:Iron-Binding Proteins; D020543:Proteome; D029702:Schizosaccharomyces pombe Proteins; D000096923:Frataxin; C468287:Pfh1 protein, S pombe