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PMID: 12868958 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Biochemical journal ·Vol. 375 ·No. Pt 2 ·2003-10-15 ·Pages 247-54

Santos R, Dancis A, Eide D, Camadro JM, Lesuisse E

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.

MeSH Terms
Cell Division/drug effects,genetics Dose-Response Relationship, Drug Drug Resistance, Fungal/genetics Gene Expression Regulation, Fungal Heme/biosynthesis Hydrogen Peroxide/pharmacology Iron/metabolism Iron-Binding Proteins/genetics,metabolism Iron-Sulfur Proteins/metabolism Mutation Oligonucleotide Array Sequence Analysis Phenotype Saccharomyces cerevisiae/drug effects,genetics,metabolism Zinc/metabolism,pharmacology
Chemicals
Iron-Binding Proteins Iron-Sulfur Proteins frataxin Heme Hydrogen Peroxide Iron Zinc
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Santos Renata
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
Eide David
Camadro Jean-Michel
Lesuisse Emmanuel
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
1470-8728
DOI
10.1042/BJ20030835
Published
2003-10-15
Pages
247-54
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1223691
Subset
IM
Grants
NIDDK NIH HHS · DK53953 · United States
NIGMS NIH HHS · GM56285 · United States
External Links
PubMed source DOI: 10.1042/BJ20030835 PMC Full Text View journal details
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