Mitochondrial control of iron homeostasis. A genome wide analysis of gene expression in a yeast frataxin-deficient strain.
Deletion of YFH1, the yeast frataxin homologue gene, elicits mitochondrial iron accumulation and alters cellular iron homeostasis. Here, we report a genome wide analysis of gene expression in a yfh1(DeltaYFH1) deleted strain. Frataxin deficiency results in enhanced expression of some 70 genes including a set of genes, called the iron regulon, that are under the control of the iron-sensing transcription factor AFT1. Five new AFT1-dependent genes, YOR382w, YOR383c, YDR534c, YLR136c, and YLR205c were found. The first three genes presumably encode cell-wall glycosylphosphatidylinositol anchor proteins and exhibit a 30-100-fold increased expression. The triple deletion of these genes decreases efficiency in utilization of the iron of ferrioxamine B by the yeast cell. YLR136c bears homology to tristetraproline proteins, which are post-transcriptional regulators in mammalian cells. Deletion of YLR136c increases the mRNA levels of iron regulon members. YLR205c bears homology to heme oxygenases. Our data show that frataxin deficiency elicits iron mobilization from all iron sources in an AFT1-dependent manner. Wild-type and DeltaYFH1 glycerol-grown cells exhibit similar high respiration rates, no mitochondrial iron accumulation, and high expression of the iron regulon, suggesting that under these conditions little iron is extruded from mitochondria. These data suggest that the activity of Yfh1p is not essential in cells grown on glycerol. This study has also revealed unexpected links between mitochondria and remote metabolic pathways since frataxin deficiency also enhances the expression of genes such as HSP30, that escape to AFT1 control. Finally, no oxidative stress gene is induced.
Foury
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Unité de Biochimie Physiologique, Place Croix du Sud, 2-20, 1348 Louvain-la-Neuve, Belgium. foury@fysa.ucl.ac.be
Talibi
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D002570:Ceruloplasmin / Q000235:genetics; D005990:Glycerol / Q000494:pharmacology; D006706:Homeostasis; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins; D008928:Mitochondria / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D018085:Regulon; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D015854:Up-Regulation; D000096923:Frataxin
D002570:Ceruloplasmin; D005990:Glycerol; D007501:Iron; D033862:Iron-Binding Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D000096923:Frataxin; C085513:FET3 protein, S cerevisiae