title: Defects in Mitochondrial Iron-Sulfur Cluster Assembly Induce Cysteine S-Polythiolation on Iron-Sulfur Apoproteins.
abstract: Mitochondria play a central role in the maturation of proteins with iron-sulfur (Fe/S) clusters. During their biogenesis, the apoforms of Fe/S proteins expose unprotected Fe/S cluster-coordinating cysteine side chains, rendering them vulnerable to oxidative modifications that interfere with subsequent Fe/S cluster insertion. Whether and how cells protect these delicate cysteine residues are unknown.
  
  
  
  In this study, we show that sulfhydryl groups of Fe/S cluster-coordinating cysteine residues of mitochondrial Fe/S apoproteins acquire cyclic S-polythiol modifications. These adducts are the result of persulfide addition, followed by a subsequent oxidation step. These modifications not only accumulate upon defects in the early stages of the mitochondrial Fe/S cluster assembly system but are also found in wild-type cells under normal growth conditions. They are, however, not found on Fe/S apoproteins in the cytosol.
  
  
  
  Our work describes a novel in vivo chemical modification of cysteine side chains in mitochondrial Fe/S apoproteins. These cyclic S-polythiolation adducts are resistant to oxidation, yet can be removed by reductive cleavage, suggesting that they serve as a reversible protection device for cysteine ligands sensitive to oxidative modification. Antioxid. Redox Signal. 25, 28-40.
authors.affiliation: 1 Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg , Marburg, Germany .
authors.forename: Stefan
authors.initials: S
authors.lastname: Christ
authors.affiliation: 2 Institute for Biochemistry and Pathobiochemistry-Microbial Biochemistry, Ruhr-Universität Bochum , Bochum, Germany .
authors.forename: Lars I
authors.initials: LI
authors.lastname: Leichert
authors.affiliation: 1 Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg , Marburg, Germany .
authors.forename: Anna
authors.initials: A
authors.lastname: Willms
authors.affiliation: 1 Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg , Marburg, Germany .|3 LOEWE Zentrum für Synthetische Mikrobiologie SYNMIKRO , Marburg, Germany .
authors.forename: Roland
authors.initials: R
authors.lastname: Lill
authors.affiliation: 1 Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg , Marburg, Germany .
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mühlenhoff
mesh_terms: D001059:Apoproteins / Q000737:chemistry / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D007501:Iron / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008928:Mitochondria / Q000378:metabolism; D008958:Models, Molecular; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism*; D013455:Sulfur / Q000378:metabolism
chemical_list: D001059:Apoproteins; D007506:Iron-Sulfur Proteins; D008024:Ligands; D013438:Sulfhydryl Compounds; D013455:Sulfur; D007501:Iron; D003545:Cysteine