Specialized Function of Yeast Isa1 and Isa2 Proteins in the Maturation of Mitochondrial [4Fe-4S] Proteins

摘要: Most eukaryotes contain iron-sulfur cluster (ISC) assembly proteins related to Saccharomyces cerevisiae Isa1 and Isa2. We show here that but not Isa2 can be functionally replaced by the bacterial relatives IscA, SufA, ErpA. The specific function of these "A-type" ISC within framework mitochondrial Fe/S protein biogenesis is still unresolved. In a comprehensive in vivo analysis, we S. form complex required for maturation [4Fe-4S] proteins, including aconitase homoaconitase. contrast, Isa1-Isa2 were dispensable generation [2Fe-2S] cytosolic proteins. Targeting ferredoxins yeast mitochondria further supported this specificity. are shown bind iron vivo, yet Isa1-Isa2-bound was needed as donor de novo on general scaffold Isu1-Isu2. Upon depletion factor Iba57, which specifically interacts with Isa2, or absence major aconitase, accumulated Isa These results suggest bound synthesis clusters their insertion into apoproteins reaction mediated Iba57. Taken together, findings define Isa1, Iba57 specialized, late-acting subsystem dedicated