The budding yeast Saccharomyces cerevisiae responds to growth in limiting amounts of iron by activating the transcription factor Aft1p and expressing a set of genes that ameliorate the effects of iron deprivation. Analysis of iron-regulated gene expression using cDNA microarrays has revealed the set of genes controlled by iron and Aft1p. Many of these genes are involved in the uptake of siderophore-bound iron from the environment. One family of genes, FIT1, FIT2 and FIT3, codes for mannoproteins that are incorporated into the cell wall via glycosylphosphatidylinositol anchors. These genes are involved in the retention of siderophore-iron in the cell wall. Siderophore-bound iron can be taken up into the cell via two genetically separable systems. One system requires the reduction and release of the iron from the siderophore prior to uptake by members of the Fre family of plasma-membrane metalloreductases. Following reduction and release from the siderophore, the iron is then taken up via the high-affinity ferrous transport system. A set of transporters that specifically recognizes siderophore-iron chelates is also expressed under conditions of iron deprivation. These transporters, encoded by ARN1, ARN2/TAF1, ARN3/SIT1 and ARN4/ENB1, facilitate the uptake of both hydroxamate- and catecholate-type siderophores. The Arn transporters are expressed in intracellular vesicles that correspond to the endosomal compartment, which suggests that intracellular trafficking of the siderophore and/or its transporter may be important for uptake.

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