A role for iron-sulfur clusters in the regulation of transcription factor Yap5-dependent high iron transcriptional responses in yeast.
Yeast respond to increased cytosolic iron by activating the transcription factor Yap5 increasing transcription of CCC1, which encodes a vacuolar iron importer. Using a genetic screen to identify genes involved in Yap5 iron sensing, we discovered that a mutation in SSQ1, which encodes a mitochondrial chaperone involved in iron-sulfur cluster synthesis, prevented expression of Yap5 target genes. We demonstrated that mutation or reduced expression of other genes involved in mitochondrial iron-sulfur cluster synthesis (YFH1, ISU1) prevented induction of the Yap5 response. We took advantage of the iron-dependent catalytic activity of Pseudaminobacter salicylatoxidans gentisate 1,2-dioxygenase expressed in yeast to measure changes in cytosolic iron. We determined that reductions in iron-sulfur cluster synthesis did not affect the activity of cytosolic gentisate 1,2-dioxygenase. We show that loss of activity of the cytosolic iron-sulfur cluster assembly complex proteins or deletion of cytosolic glutaredoxins did not reduce expression of Yap5 target genes. These results suggest that the high iron transcriptional response, as well as the low iron transcriptional response, senses iron-sulfur clusters.
Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132.
Liangtao
L
Li
Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132.
Ren
R
Miao
Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132.
Sophie
S
Bertram
Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132.
Xuan
X
Jia
Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132.
Diane M
DM
Ward
Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132. Electronic address: jerry.kaplan@path.utah.edu.
Jerry
J
Kaplan
D050976:Basic-Leucine Zipper Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010084:Oxidation-Reduction; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D013455:Sulfur / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*
D050976:Basic-Leucine Zipper Transcription Factors; D018840:HSP70 Heat-Shock Proteins; C094046:IFH1 protein, S cerevisiae; C121520:ISU1 protein, S cerevisiae; D024101:Mitochondrial Proteins; C115913:SSQ1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; C526591:Yap5 protein, S cerevisiae; D013455:Sulfur; D007501:Iron