Novel insights into iron metabolism by integrating deletome and transcriptome analysis in an iron deficiency model of the yeast Saccharomyces cerevisiae

Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California 94720, USA.
BMC Genomics (Impact Factor: 3.99). 04/2009; 10(1):130. DOI: 10.1186/1471-2164-10-130
Source: PubMed


Iron-deficiency anemia is the most prevalent form of anemia world-wide. The yeast Saccharomyces cerevisiae has been used as a model of cellular iron deficiency, in part because many of its cellular pathways are conserved. To better understand how cells respond to changes in iron availability, we profiled the yeast genome with a parallel analysis of homozygous deletion mutants to identify essential components and cellular processes required for optimal growth under iron-limited conditions. To complement this analysis, we compared those genes identified as important for fitness to those that were differentially-expressed in the same conditions. The resulting analysis provides a global perspective on the cellular processes involved in iron metabolism.
Using functional profiling, we identified several genes known to be involved in high affinity iron uptake, in addition to novel genes that may play a role in iron metabolism. Our results provide support for the primary involvement in iron homeostasis of vacuolar and endosomal compartments, as well as vesicular transport to and from these compartments. We also observed an unexpected importance of the peroxisome for growth in iron-limited media. Although these components were essential for growth in low-iron conditions, most of them were not differentially-expressed. Genes with altered expression in iron deficiency were mainly associated with iron uptake and transport mechanisms, with little overlap with those that were functionally required. To better understand this relationship, we used expression-profiling of selected mutants that exhibited slow growth in iron-deficient conditions, and as a result, obtained additional insight into the roles of CTI6, DAP1, MRS4 and YHR045W in iron metabolism.
Comparison between functional and gene expression data in iron deficiency highlighted the complementary utility of these two approaches to identify important functional components. This should be taken into consideration when designing and analyzing data from these type of studies. We used this and other published data to develop a molecular interaction network of iron metabolism in yeast.

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    • "The first is to limit the available iron in the medium by chelators. For work with yeasts like S. cerevisiae and Schizosaccharomyces pombe, iron-chelators such as 2,2′-dipyridyl and bathophenanthroline disulfonic acid, are often used to generate a state of poor iron nutrition in vivo (Eide et al., 1996; Pelletier et al., 2005; Mercier et al., 2006; Jo et al., 2009). Some studies with plants like Arabidopsis thaliana have combined the use of chelators like ferrozine with the strategy of creating iron deficiency by omitting iron from the media (Vert et al., 2002; Lanquar et al., 2005; Yang et al., 2010). "
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    • "The yeast Saccharomyces cerevisiae has proved to be a powerful model for the study of mineral nutrient and trace element homeostasis, for recent reviews see [1-4]. The availability of full genome deletion and open reading frame (ORF) overexpression collections [5-7] have further enhanced the power of yeast as a model system, and these genome-wide tools have already been applied to the study of mineral nutrient and trace element homeostasis, indirectly by studying the growth effects of elevated transition metals [2,8], B [9], selenite [10], and Fe [11] and Zn [12] deficiency. Studies have also been undertaken in which accumulation of Fe [13], Cs, Sr [14], and P [15] have been directly quantified in yeast cells. "
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    • "Also, conventional growth assays (on elevated calcium or zinc) do not differentiate between wild-type yeast and yeast lacking STV1, as the vacuolar isoform compensates for a loss of the Stv1p-containing complex (Figure 3A). However, a recent report described a phenotypic difference between wild-type yeast and stv1∆ mutant yeast on media containing the iron chelator, BPS (Jo et al., 2009). "
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