Disruption of iron homeostasis in Saccharomyces cerevisiae by high zinc levels: a genome-wide study.
Zinc is an essential metal that, when in excess, can be deleterious to the cell. Therefore, homeostatic mechanisms for this cation must be finely tuned. To better understand the response of yeast in front of an excess of zinc, we screened a systematic deletion mutant library for altered growth in the presence of 6 mM zinc. Eighty-nine mutants exhibited increased zinc sensitivity, including many genes involved in vacuolar assembling and biogenesis. Interestingly, a mutant lacking the Aft1 transcription factor, required for the transcriptional response to iron starvation, was found to be highly sensitive to zinc. Genome-wide transcriptional profiling revealed that exposure to 5 mM ZnCl(2) results in rapid increase in the expression of numerous chaperones required for proper protein folding or targeting to vacuole and mitochondria, as well as genes involved in stress response (mainly oxidative), sulphur metabolism and some components of the iron regulon. The effect of the lack of Aft1 both in the absence and in the presence of zinc overload was also investigated. Exposure to high zinc generated reactive oxygen species and markedly decreased glutathione content. Interestingly, zinc excess results in decreased intracellular iron content and aconitase and cytochrome c activities in stationary-phase cultures. These findings suggest that high zinc levels may alter the assembly and/or function of iron-sulphur-containing proteins, as well as the biosynthesis of haem groups, thus establishing a link between zinc, iron and sulphur metabolism.
Pagani
M Ayelen
MA
Departament de Genètica, Universitat de Barcelona, Barcelona, Spain.
Casamayor
Antonio
A
Serrano
Raquel
R
Atrian
Sílvia
S
Ariño
Joaquín
J
D000154:Aconitate Hydratase / Q000032:analysis / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D020869:Gene Expression Profiling; D005800:Genes, Fungal; D016681:Genome, Fungal; D005978:Glutathione / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics; D007501:Iron / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D015032:Zinc / Q000378:metabolism / Q000633:toxicity*; D017967:Zinc Compounds / Q000494:pharmacology
C090297:AFT1 protein, S cerevisiae; D002712:Chlorides; D007506:Iron-Sulfur Proteins; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D017967:Zinc Compounds; C016837:zinc chloride; D045304:Cytochromes c; D007501:Iron; D000154:Aconitate Hydratase; D005978:Glutathione; D015032:Zinc