title: Systematic analysis of the twin cx(9)c protein family.
abstract: The Mia40-Erv1 disulfide relay system is of high importance for mitochondrial biogenesis. Most so far identified substrates of this machinery contain either two cysteine-x(3)-cysteine (twin Cx(3)C) or two cysteine-x(9)-cysteine (twin Cx(9)C) motifs. While the first group is composed of well-characterized components of the mitochondrial import machinery, the molecular function of twin Cx(9)C proteins still remains unclear. To systematically characterize this protein family, we performed a database search to identify the full complement of Cx(9)C proteins in yeast. Thereby, we identified 14 potential family members, which, with one exception, are conserved among plants, fungi, and animals. Among these, three represent novel proteins, which we named Cmc2 to 4 (for Cx(9)C motif-containing protein) and which we demonstrated to be dependent for import on the Mia40-Erv1 disulfide relay. By testing deletion mutants of all 14 proteins for function of the respiratory chain, we found a critical function of most of these proteins for the assembly or stability of respiratory chain complexes. Our data suggest that already early during the evolution of eukaryotic cells, a multitude of twin Cx(9)C proteins developed, which exhibit largely nonredundant roles critical for the biogenesis of enzymes of the respiratory chain in mitochondria.
authors.affiliation: University of Kaiserslautern, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Longen
authors.forename: Melanie
authors.initials: M
authors.lastname: Bien
authors.forename: Karl
authors.initials: K
authors.lastname: Bihlmaier
authors.forename: Christine
authors.initials: C
authors.lastname: Kloeppel
authors.forename: Frank
authors.initials: F
authors.lastname: Kauff
authors.forename: Miriam
authors.initials: M
authors.lastname: Hammermeister
authors.forename: Benedikt
authors.initials: B
authors.lastname: Westermann
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Herrmann
authors.forename: Jan
authors.initials: J
authors.lastname: Riemer
mesh_terms: D000595:Amino Acid Sequence; D019295:Computational Biology; D016681:Genome, Fungal / Q000235:genetics; D008856:Microscopy, Fluorescence; D033681:Mitochondrial Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: C495320:MIA40 protein, S cerevisiae; C105693:MRP10 protein, S cerevisiae; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D050862:Oxidoreductases Acting on Sulfur Group Donors; C073790:ERV1 protein, S cerevisiae