title: MR-1S Interacts with PET100 and PET117 in Module-Based Assembly of Human Cytochrome c Oxidase.
abstract: The biogenesis of human cytochrome c oxidase (COX) is an intricate process in which three mitochondrial DNA (mtDNA)-encoded core subunits are assembled in a coordinated way with at least 11 nucleus-encoded subunits. Many chaperones shared between yeast and humans are involved in COX assembly. Here, we have used a MT-CO3 mutant cybrid cell line to define the composition of assembly intermediates and identify new human COX assembly factors. Quantitative mass spectrometry analysis led us to modify the assembly model from a sequential pathway to a module-based process. Each module contains one of the three core subunits, together with different ancillary components, including HIGD1A. By the same analysis, we identified the short isoform of the myofibrillogenesis regulator 1 (MR-1S) as a new COX assembly factor, which works with the highly conserved PET100 and PET117 chaperones to assist COX biogenesis in higher eukaryotes.
authors.affiliation: MRC Mitochondrial Biology Unit, Cambridge CB2 0XY, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Vidoni
authors.affiliation: MRC Mitochondrial Biology Unit, Cambridge CB2 0XY, UK.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Harbour
authors.affiliation: Radboud Center for Mitochondrial Medicine, Radboud University Medical Center, 6525 Nijmegen, the Netherlands.
authors.forename: Sergio
authors.initials: S
authors.lastname: Guerrero-Castillo
authors.affiliation: MRC Mitochondrial Biology Unit, Cambridge CB2 0XY, UK.
authors.forename: Alba
authors.initials: A
authors.lastname: Signes
authors.affiliation: MRC Mitochondrial Biology Unit, Cambridge CB2 0XY, UK.
authors.forename: Shujing
authors.initials: S
authors.lastname: Ding
authors.affiliation: MRC Mitochondrial Biology Unit, Cambridge CB2 0XY, UK.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Fearnley
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.affiliation: Unit of Molecular Neurogenetics, Fondazione Istituto Neurologico Carlo Besta, 20133 Milan, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Tiranti
authors.affiliation: Radboud Center for Mitochondrial Medicine, Radboud University Medical Center, 6525 Nijmegen, the Netherlands.
authors.forename: Susanne
authors.initials: S
authors.lastname: Arnold
authors.affiliation: MRC Mitochondrial Biology Unit, Cambridge CB2 0XY, UK. Electronic address: emfvb2@mrc-mbu.cam.ac.uk.
authors.forename: Erika
authors.initials: E
authors.lastname: Fernandez-Vizarra
authors.affiliation: MRC Mitochondrial Biology Unit, Cambridge CB2 0XY, UK. Electronic address: mdz21@mrc-mbu.cam.ac.uk.
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000235:genetics; D003576:Electron Transport Complex IV / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004272:DNA, Mitochondrial; C413044:KAT14 protein, human; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D009124:Muscle Proteins; C587424:PET100 protein, human; C495444:PNKD protein, human; D021122:Protein Subunits; D003576:Electron Transport Complex IV
keywords: COX assembly; MR-1S; PET100; PET117; SILAC; complexome profiling; cytochrome c oxidase; mitochondrial respiratory chain; myofibrillogenesis regulator 1 short isoform