Persulfide formation on mitochondrial cysteine desulfurase: enzyme activation by a eukaryote-specific interacting protein and Fe-S cluster synthesis

Cysteine desulfurases abstract sulfur from the substrate cysteine, generate a covalent persulfide on the active site cysteine of the enzyme, and then donate the persulfide sulfur to various recipients such as Fe-S clusters. In Saccharomyces cerevisiae, the Nfs1p protein is the only known cysteine desulfurase, and it forms a complex with Isd11p (Nfs1p . Isd11p). Both of these proteins are found primarily in mitochondria and both are essential for cell viability. In the present study we show, using the results of experiments with isolated mitochondria and purified proteins, that Isd11p is required for the cysteine desulfurase activity of Nfs1p. Whereas Nfs1p by itself was inactive, the Nfs1p . Isd11p complex formed persulfide and was active as a cysteine desulfurase. In the