title: The mitochondrial Hsp70 chaperone Ssq1 facilitates Fe/S cluster transfer from Isu1 to Grx5 by complex formation.
abstract: The mitochondrial Hsp70 chaperone Ssq1 plays a dedicated role in the maturation of iron-sulfur (Fe/S) proteins, an essential process of mitochondria. Similar to its bacterial orthologue HscA, Ssq1 binds to the scaffold protein Isu1, thereby facilitating dissociation of the newly synthesized Fe/S cluster on Isu1 and its transfer to target apoproteins. Here we use in vivo and in vitro approaches to show that Ssq1 also interacts with the monothiol glutaredoxin 5 (Grx5) at a binding site different from that of Isu1. Grx5 binding does not stimulate the ATPase activity of Ssq1 and is most pronounced for the ADP-bound form of Ssq1, which interacts with Isu1 most tightly. The vicinity of Isu1 and Grx5 on the Hsp70 chaperone facilitates rapid Fe/S cluster transfer from Isu1 to Grx5. Grx5 and its bound Fe/S cluster are required for maturation of all cellular Fe/S proteins, regardless of the type of bound Fe/S cofactor and subcellular localization. Hence Grx5 functions as a late-acting component of the core Fe/S cluster (ISC) assembly machinery linking the Fe/S cluster synthesis reaction on Isu1 with late assembly steps involving Fe/S cluster targeting to dedicated apoproteins.
authors.affiliation: Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg, 35032 Marburg, Germany.
authors.forename: Marta A
authors.initials: MA
authors.lastname: Uzarska
authors.forename: Rafal
authors.initials: R
authors.lastname: Dutkiewicz
authors.forename: Sven-Andreas
authors.initials: SA
authors.lastname: Freibert
authors.forename: Roland
authors.initials: R
authors.lastname: Lill
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mühlenhoff
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001665:Binding Sites; D003600:Cytosol / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D054477:Glutaredoxins / Q000235:genetics / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D047468:Immunoprecipitation; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D054477:Glutaredoxins; C528773:Grx5 protein, S cerevisiae; D018840:HSP70 Heat-Shock Proteins; C121520:ISU1 protein, S cerevisiae; D007506:Iron-Sulfur Proteins; C115914:JAC1 protein, S cerevisiae; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; C115913:SSQ1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate