title: An intragenic suppressor in the cytochrome c oxidase I gene of mouse mitochondrial DNA.
abstract: We report here the identification of a cell line containing single and double missense mutations in cytochrome c oxidase (COX) subunit I gene of mouse mitochondrial DNA. When present in homoplasmy, the single mutant displays a normal complex IV assembly but a significantly reduced COX activity, while the double mutant almost completely compensates the functional defect of the first mutation. We discuss the potential structural consequences of those mutations based on the modeled structure of mouse complex IV. Based on genetic, biochemical and molecular analyses of cultured mouse cells we infer that: (i) deleterious mutations can arise and become predominant; (ii) cultured cells can maintain several mtDNA haplotypes at stable frequencies; (iii) the respiratory chain has little spare COX capacity; and (iv) the size of a cavity in the vicinity of Val421 in CO I of animal COX may affect the function of the enzyme.
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Miguel Servet 177, 50013 Zaragoza, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Acín-Pérez
authors.forename: María Pilar
authors.initials: MP
authors.lastname: Bayona-Bafaluy
authors.forename: Marta
authors.initials: M
authors.lastname: Bueno
authors.forename: Claudia
authors.initials: C
authors.lastname: Machicado
authors.forename: Patricio
authors.initials: P
authors.lastname: Fernández-Silva
authors.forename: Acisclo
authors.initials: A
authors.lastname: Pérez-Martos
authors.forename: Julio
authors.initials: J
authors.lastname: Montoya
authors.forename: M J
authors.initials: MJ
authors.lastname: López-Pérez
authors.forename: Javier
authors.initials: J
authors.lastname: Sancho
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Enríquez
mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D006239:Haplotypes; D051379:Mice; D009154:Mutation; D010101:Oxygen Consumption / Q000235:genetics / Q000502:physiology; D010802:Phylogeny; D013489:Suppression, Genetic
chemical_list: D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV