Saccharomyces cerevisiae ISU1 and ISU2: members of a well-conserved gene family for iron-sulfur cluster assembly

Abstract

Recent studies in bacteria and eukaryotes have led to the identification of several new genes implicated in the biogenesis of iron-sulfur (Fe/S) cluster-containing proteins. This report focuses on two genes of bakers yeast Saccharomyces cerevisiae, ISU1 and ISU2, which encode homologues to bacterial IscU and NifU, potential iron-binding or cluster-assembly proteins. As with other yeast genes implicated in Fe/S protein assembly, deletion of either ISU1 or ISU2 results in increased accumulation of iron within the mitochondria, loss of activity of the [4Fe-4S] aconitase enzyme, and suppression of oxidative damage in cells lacking cytosolic copper/zinc superoxide dismutase. Both genes are induced in strains expressing an activated allele of Aft1p, the iron-sensing transcription factor, suggesting that they are regulated by the iron status of the cell. Immunoblotting studies using an antibody directed against Escherichia coli IscU reveal that both Isu1p and Isu2p are localized primarily in the mitochondria and that Isu1p is the predominant form expressed under all growth conditions tested. The possible role of the Isu proteins in the assembly and/or repair of Fe/S clusters is discussed.