The mitochondrial Hsp70 chaperone Ssq1 facilitates Fe/S cluster transfer from Isu1 to Grx5 by complex formation |
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| Authors: | Marta A Uzarska Rafal Dutkiewicz Sven-Andreas Freibert Roland Lill Ulrich Mühlenhoff |
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| Institution: | Cornell University;aInstitut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg, 35032 Marburg, Germany;bDepartment of Molecular and Cellular Biology, Faculty of Biotechnology, University of Gdansk, 80-822 Gdansk, Poland;cMax-Planck-Institut für Terrestrische Mikrobiologie and;dLOEWE Zentrum für Synthetische Mikrobiologie SYNMIKRO, 35043 Marburg, Germany |
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| 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. |
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