An intragenic suppressor in the cytochrome c oxidase I gene of mouse mitochondrial DNA.
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.
Acín-Pérez
Rebeca
R
Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Miguel Servet 177, 50013 Zaragoza, Spain.
Bayona-Bafaluy
María Pilar
MP
Bueno
Marta
M
Machicado
Claudia
C
Fernández-Silva
Patricio
P
Pérez-Martos
Acisclo
A
Montoya
Julio
J
López-Pérez
M J
MJ
Sancho
Javier
J
Enríquez
José Antonio
JA
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
D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV