Jo WJ~Vulpe CD, 2007

Pubmed ID 17785683
Title Identification of genes involved in the toxic response of Saccharomyces cerevisiae against iron and copper overload by parallel analysis of deletion mutants.
Authors William J Jo, Alex Loguinov, Michelle Chang, Henri Wintz, Corey Nislow, Adam P Arkin, Guri Giaever, Chris D Vulpe
Abstract Iron and copper are essential nutrients for life as they are required for the function of many proteins but can be toxic if present in excess. Accumulation of these metals in the human body as a consequence of overload disorders and/or high environmental exposures has detrimental effects on health. The budding yeast Saccharomyces cerevisiae is an accepted cellular model for iron and copper metabolism in humans primarily because of the high degree of conservation between pathways and proteins involved. Here we report a systematic screen using yeast deletion mutants to identify genes involved in the toxic response to growth-inhibitory concentrations of iron and copper sulfate. We aimed to understand the cellular responses to toxic concentrations of these two metals by analyzing the different subnetworks and biological processes significantly enriched with these genes. Our results indicate the presence of two different detoxification pathways for iron and copper that converge toward the vacuole. The product of several of the identified genes in these pathways form molecular complexes that are conserved in mammals and include the retromer, endosomal sorting complex required for transport (ESCRT) and AP-3 complexes, suggesting that the mechanisms involved can be extrapolated to humans. Our data also suggest a disruption in ion homeostasis and, in particular, of iron after copper exposure. Moreover, the identification of treatment-specific genes associated with biological processes such as DNA double-strand break repair for iron and tryptophan biosynthesis for copper suggests differences in the mechanisms by which these two metals are toxic at high concentrations.
Citation Toxicol. Sci. 2008; 101:140-51

Datasets

Download the list of datasets
Paper Phenotype Condition Medium Collection Tested mutants Data Details
Jo WJ~Vulpe CD, 2007 growth (relative abundance in pooled culture) iron sulfate pentahydrate [5 mM], time [15 gen] YPD hom ~4,757 Quantitative only for hits
Jo WJ~Vulpe CD, 2007 growth (relative abundance in pooled culture) copper(II) sulfate heptahydrate [10 mM], time [15 gen] YPD hom ~4,757 Quantitative only for hits

Curation history

Data

June 10, 2016 To request.
June 10, 2016 Request sent.
Aug. 17, 2016 Request sent.
April 25, 2017 Request abandoned.
April 25, 2017 Ready to load.
May 2, 2017 Loaded.

Tested strains

June 10, 2016 To request.
June 10, 2016 Request sent.
Aug. 17, 2016 Request sent.
April 25, 2017 Request abandoned.