title: An interaction between frataxin and Isu1/Nfs1 that is crucial for Fe/S cluster synthesis on Isu1.
abstract: Depletion of the mitochondrial matrix protein frataxin is the molecular cause of the neurodegenerative disease Friedreich ataxia. The function of frataxin is unclear, although recent studies have suggested a function of frataxin (yeast Yfh1) in iron/sulphur (Fe/S) protein biogenesis. Here, we show that Yfh1 specifically binds to the central Fe/S-cluster (ISC)-assembly complex, which is composed of the scaffold protein Isu1 and the cysteine desulphurase Nfs1. Association between Yfh1 and Isu1/Nfs1 was markedly increased by ferrous iron, but did not depend on ISCs on Isu1. Functional analyses in vivo showed an involvement of Yfh1 in de novo ISC synthesis on Isu1. Our data demonstrate a crucial function of Yfh1 in Fe/S protein biogenesis by defining its function in an early step of this essential process. The iron-dependent binding of Yfh1 to Isu1/Nfs1 suggests a role of frataxin/Yfh1 in iron loading of the Isu scaffold proteins.
authors.affiliation: Institute for Cytobiology and Cytopathology, Philipps-Universität Marburg, Robert-Koch Strasse 6, D-35033 Marburg, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Gerber
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mühlenhoff
authors.forename: Roland
authors.initials: R
authors.lastname: Lill
mesh_terms: D033862:Iron-Binding Proteins / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000096:biosynthesis*; D024101:Mitochondrial Proteins; D011233:Precipitin Tests; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013466:Sulfurtransferases; D000096923:Frataxin
chemical_list: D033862:Iron-Binding Proteins; D007506:Iron-Sulfur Proteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D013466:Sulfurtransferases; D000096923:Frataxin; C121520:ISU1 protein, S cerevisiae; C115912:NFS1 protein, S cerevisiae