title: Oms1 associates with cytochrome c oxidase assembly intermediates to stabilize newly synthesized Cox1.
abstract: The mitochondrial cytochrome c oxidase assembles in the inner membrane from subunits of dual genetic origin. The assembly process of the enzyme is initiated by membrane insertion of the mitochondria-encoded Cox1 subunit. During complex maturation, transient assembly intermediates, consisting of structural subunits and specialized chaperone-like assembly factors, are formed. In addition, cofactors such as heme and copper have to be inserted into the nascent complex. To regulate the assembly process, the availability of Cox1 is under control of a regulatory feedback cycle in which translation of COX1 mRNA is stalled when assembly intermediates of Cox1 accumulate through inactivation of the translational activator Mss51. Here we isolate a cytochrome c oxidase assembly intermediate in preparatory scale from coa1Δ mutant cells, using Mss51 as bait. We demonstrate that at this stage of assembly, the complex has not yet incorporated the heme a cofactors. Using quantitative mass spectrometry, we define the protein composition of the assembly intermediate and unexpectedly identify the putative methyltransferase Oms1 as a constituent. Our analyses show that Oms1 participates in cytochrome c oxidase assembly by stabilizing newly synthesized Cox1.
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, D-37073 Göttingen, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Bareth
authors.affiliation: Bioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, D-37077 Göttingen, Germany.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Nikolov
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, D-37073 Göttingen, Germany.
authors.forename: Isotta
authors.initials: I
authors.lastname: Lorenzi
authors.affiliation: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Hildenbeutel
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, D-37073 Göttingen, Germany.
authors.forename: David U
authors.initials: DU
authors.lastname: Mick
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, D-37073 Göttingen, Germany.
authors.forename: Christin
authors.initials: C
authors.lastname: Helbig
authors.affiliation: Bioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, D-37077 Göttingen, Germany Bioanalytik Group, Department of Clinical Chemistry, University Medical Center Göttingen, D-37075 Göttingen, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Urlaub
authors.affiliation: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Ott
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, D-37073 Göttingen, Germany Max Planck Institute for Biophysical Chemistry, D-37077 Göttingen, Germany Peter.Rehling@medizin.uni-goettingen.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Rehling
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, D-37073 Göttingen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Dennerlein
mesh_terms: D045304:Cytochromes c / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D008565:Membrane Proteins / Q000378:metabolism; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; C519191:Mss51 protein, S cerevisiae; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D045304:Cytochromes c; C526453:Cox1 protein, S cerevisiae; D003576:Electron Transport Complex IV; D008780:Methyltransferases; C495319:OMS1 protein, S cerevisiae