title: Mitochondrial Bol1 and Bol3 function as assembly factors for specific iron-sulfur proteins.
abstract: Assembly of mitochondrial iron-sulfur (Fe/S) proteins is a key process of cells, and defects cause many rare diseases. In the first phase of this pathway, ten Fe/S cluster (ISC) assembly components synthesize and insert [2Fe-2S] clusters. The second phase is dedicated to the assembly of [4Fe-4S] proteins, yet this part is poorly understood. Here, we characterize the BOLA family proteins Bol1 and Bol3 as specific mitochondrial ISC assembly factors that facilitate [4Fe-4S] cluster insertion into a subset of mitochondrial proteins such as lipoate synthase and succinate dehydrogenase. Bol1-Bol3 perform largely overlapping functions, yet cannot replace the ISC protein Nfu1 that also participates in this phase of Fe/S protein biogenesis. Bol1 and Bol3 form dimeric complexes with both monothiol glutaredoxin Grx5 and Nfu1. Complex formation differentially influences the stability of the Grx5-Bol-shared Fe/S clusters. Our findings provide the biochemical basis for explaining the pathological phenotypes of patients with mutations in BOLA3.
authors.affiliation: Institut für Zytobiologie und Zytopathologie, Philipps-Universität, Marburg, Germany.
authors.forename: Marta A
authors.initials: MA
authors.lastname: Uzarska
authors.affiliation: Magnetic Resonance Center CERM, University of Florence, Florence, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Nasta
authors.affiliation: Institut für Zytobiologie und Zytopathologie, Philipps-Universität, Marburg, Germany.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Weiler
authors.affiliation: Institut für Zytobiologie und Zytopathologie, Philipps-Universität, Marburg, Germany.
authors.forename: Farah
authors.initials: F
authors.lastname: Spantgar
authors.affiliation: Magnetic Resonance Center CERM, University of Florence, Florence, Italy.|Department of Chemistry, University of Florence, Florence, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Ciofi-Baffoni
authors.affiliation: Magnetic Resonance Center CERM, University of Florence, Florence, Italy.|Department of Chemistry, University of Florence, Florence, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Saviello
authors.affiliation: Magnetic Resonance Center CERM, University of Florence, Florence, Italy.|Department of Chemistry, University of Florence, Florence, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Gonnelli
authors.affiliation: Institut für Zytobiologie und Zytopathologie, Philipps-Universität, Marburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mühlenhoff
authors.affiliation: Magnetic Resonance Center CERM, University of Florence, Florence, Italy.|Department of Chemistry, University of Florence, Florence, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Banci
authors.affiliation: Institut für Zytobiologie und Zytopathologie, Philipps-Universität, Marburg, Germany.|LOEWE Zentrum für Synthetische Mikrobiologie SynMikro, Marburg, Germany.
authors.forename: Roland
authors.identifier: 0000-0002-8345-6518
authors.initials: R
authors.lastname: Lill
mesh_terms: D054477:Glutaredoxins / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D055503:Protein Multimerization; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: D054477:Glutaredoxins; C528773:Grx5 protein, S cerevisiae; D007506:Iron-Sulfur Proteins; D024101:Mitochondrial Proteins; C121524:NFU1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins
keywords: ISC machinery; S. cerevisiae; biochemistry; cancer biology; human; lipoic acid; metal biology; post-translational modification; respiratory chain