Zinc suppresses the iron-accumulation phenotype of Saccharomyces cerevisiae lacking the yeast frataxin homologue (Yfh1)

Biochem J. 2003 Oct 15;375(Pt 2):247-54. doi: 10.1042/BJ20030835.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Division / drug effects
  • Cell Division / genetics
  • Dose-Response Relationship, Drug
  • Drug Resistance, Fungal / genetics
  • Frataxin
  • Gene Expression Regulation, Fungal
  • Heme / biosynthesis
  • Hydrogen Peroxide / pharmacology
  • Iron / metabolism*
  • Iron-Binding Proteins / genetics*
  • Iron-Binding Proteins / metabolism
  • Iron-Sulfur Proteins / metabolism
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Zinc / metabolism
  • Zinc / pharmacology*

Substances

  • Iron-Binding Proteins
  • Iron-Sulfur Proteins
  • Heme
  • Hydrogen Peroxide
  • Iron
  • Zinc