Zinc suppresses the iron-accumulation phenotype of Saccharomyces cerevisiae lacking the yeast frataxin homologue (Yfh1).
Analysis of Saccharomyces cerevisiae cell transcriptome revealed that iron deprivation/supplementation affects genes other than those of the iron regulon (controlled by Aft proteins). Several genes regulated by zinc (induced by zinc deprivation) were induced by iron. Cells lacking the yeast frataxin homologue Yfh1 accumulate large amounts of iron in their mitochondria. We have shown that the zinc metabolism of these cells is also impaired: zinc uptake and zinc accumulation were both much lower in Delta yfh1 cells than in wild-type cells. Excess zinc in the growth medium also influenced the phenotypes of Delta yfh1 cells. It prevented the accumulation of iron in the mitochondria of Delta yfh1 cells and increased the growth rate of these cells and their resistance to oxidative stress. However, zinc did not restore the deficiency of Fe-S and haem proteins of Delta yfh1 cells. Zinc inhibited mitochondrial respiration and protected Yah1p, the mitochondrial ferredoxin. These results suggest that zinc nutrition may be important in the aetiology of Friedreich's ataxia.
Santos
Renata
R
Laboratoire d'Ingéniérie des Protéines et Contrôle Métabolique, Département de Biologie des Génomes, Institut Jacques Monod, Tour 43, Unité Mixte de Recherche 7592 CNRS-Universités Paris 6 and 7, 2 place Jussieu, F-75251 Paris cedex 05, France.
Dancis
Andrew
A
Eide
David
D
Camadro
Jean-Michel
JM
Lesuisse
Emmanuel
E
D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D025141:Drug Resistance, Fungal / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D006418:Heme / Q000096:biosynthesis; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology*; D000096923:Frataxin
D006418:Heme; D006861:Hydrogen Peroxide; D007501:Iron; D033862:Iron-Binding Proteins; D007506:Iron-Sulfur Proteins; D015032:Zinc; D000096923:Frataxin