Jo WJ, et al. (2008) Identification of genes involved in the toxic response of Saccharomyces cerevisiae against iron and copper overload by parallel analysis of deletion mutants. Toxicol Sci 101(1):140-51
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, ESCRT and AP-3 complexes, suggesting that the mechanisms involved can be extrapolated to humans. Our data also suggests 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.
|Status: Published||Type: Journal Article||PubMed ID: 17785683|
Topics addressed in this paper
- To find other papers on a gene and topic, click on the colored ball in the appropriate box.
- displays other papers with information about that topic for that gene.
- displays other papers in SGD that are associated with that topic.
The topic is addressed in these papers but does not describe a specific gene or chromosomal feature.
- To go to the Locus page for a gene, click on the gene name.