A non-essential function for yeast frataxin in iron-sulfur cluster assembly.
Friedreich's ataxia is caused by a deficit in frataxin, a small mitochondrial protein of unknown function that has been conserved during evolution. Previous studies have pointed out a role for frataxin in mitochondrial iron-sulfur (Fe-S) metabolism. Here, we have analyzed the incorporation of Fe-S clusters into yeast ferredoxin imported into isolated energized mitochondria from cells grown in the presence of glycerol, an obligatory respiratory carbon source. Similar amounts of apo-ferredoxin precursor were imported into mitochondria and processed in wild-type and yfh1-deleted (delta YF111) strains. However, the incorporation of Fe-S clusters into apo-ferredoxin was significantly reduced in delta YFH1 mitochondria. The newly assembled ferredoxin was stable, excluding the possibility that the decreased incorporation was a result of increased oxidative damage. When delta YFH1 cells were grown in raffinose medium, the formation of holo-ferredoxin was low, as a consequence of the decrease in ferredoxin precursor import into mitochondria. However, the decrease in the conversion rate of apo- into holo-ferredoxin was in the same range as for glycerol-grown cells, indicating that the extent of the defect in Fe-S protein assembly is similar under different physiological conditions. These data show that frataxin is not essential for Fe-S protein assembly, but improves the efficiency of the process. The large variations observed in the activity of Fe-S cluster proteins under different physiological conditions result from secondary defects in the physiology of delta YFH1 cells.
D003545:Cysteine / Q000378:metabolism; D066298:In Vitro Techniques; D033862:Iron-Binding Proteins / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D013462:Sulfur Radioisotopes / Q000378:metabolism; D000096923:Frataxin
D003545:Cysteine; D033862:Iron-Binding Proteins; D007506:Iron-Sulfur Proteins; D013462:Sulfur Radioisotopes; D000096923:Frataxin