title: Yap5 protein-regulated transcription of the TYW1 gene protects yeast from high iron toxicity.
abstract: The budding yeast Saccharomyces cerevisiae responds to high cytosolic iron by inducing Yap5-mediated transcription. We identified genes regulated by Yap5 in response to iron and show that one of the genes induced is TYW1, which encodes an iron-sulfur cluster enzyme that participates in the synthesis of wybutosine-modified tRNA. Strains deleted for TYW1 do not show a phenotype in standard yeast medium. In contrast, overexpression of TYW1 results in decreased cell growth and induction of the iron regulon, leading to increased expression of the high affinity iron transporters. We identified a minimal domain of S. cerevisiae Tyw1 that is sufficient to induce the iron regulon. CCC1, a vacuolar iron importer, is a Yap5-regulated gene, and deletion of either CCC1 or YAP5 resulted in high iron sensitivity. Deletion of TYW1 in a Δccc1 strain led to increased iron sensitivity. The increased iron sensitivity of Δccc1Δtyw1 could be suppressed by overexpression of iron-sulfur cluster enzymes. We conclude that the Yap5-mediated induction of TYW1 provides protection from high iron toxicity by the consumption of free cytosolic iron through the formation of protein-bound iron-sulfur clusters.
authors.affiliation: Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132.
authors.forename: Liangtao
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132.
authors.forename: Xuan
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132.
authors.forename: Diane M
authors.initials: DM
authors.lastname: Ward
authors.affiliation: Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132. Electronic address: jerry.kaplan@path.utah.edu.
authors.forename: Jerry
authors.initials: J
authors.lastname: Kaplan
mesh_terms: D000595:Amino Acid Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D007501:Iron / Q000737:chemistry; D007506:Iron-Sulfur Proteins / Q000737:chemistry; D008856:Microscopy, Fluorescence / Q000379:methods; D008928:Mitochondria / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D007506:Iron-Sulfur Proteins; D029701:Saccharomyces cerevisiae Proteins; C526591:Yap5 protein, S cerevisiae; D007501:Iron; D010088:Oxidoreductases; C569111:TYW1 protein, S cerevisiae