An essential function of the mitochondrial sulfhydryl oxidase Erv1p/ALR inthe maturation of cytosolic Fe/S proteins

Biogenesis of Fe/S clusters involves a number of essential mitochondrial pr oteins. Here, we identify the essential Erv1p of Saccharomyces cerevisia mi tochondria as a novel component that is specifically required for the matur ation of Fe/S proteins in the cytosol, but not in mitochondria. Furthermore , Erv1p was found to be important for cellular iron homeostasis. The homolo gous mammalian protein ALR ('augmenter of liver regeneration'), also termed hepatopoietin, can functionally replace defects in Erv1p and thus represen ts the mammalian orthologue of yeast Erv1p. Previously, a fragment of ALR w as reported to exhibit an activity as an extracellular hepatotrophic growth factor. Both Erv1p and full-length ALR are located in the mitochondrial in termembrane space and represent the first components of this compartment wi th a role in the biogenesis of cytosolic Fe/S proteins. It is likely that E rv1p/ALR operates downstream of the mitochondrial ABC transporter Atm1p/ABC 7/Sta1, which also executes a specific task in this essential biochemical p rocess.