Sequence analysis of the structural nuclear encoded subunits and assembly genes of cytochrome c oxidase in a cohort of 10 isolated complex IV-deficient patients revealed five mutations.
The mitochondrial oxidative phosphorylation system is composed of five multiprotein complexes. The fourth complex of this system, cytochrome c oxidase (complex IV), consists of 13 subunits: 3 encoded by mitochondrial DNA and 10 encoded by the nuclear genome. Patients with an isolated complex IV deficiency frequently harbor mutations in nuclear genes encoding for proteins necessary for the assembly of the complex. Strikingly, until now, no mutations have been detected in the nuclear encoded structural subunits of complex IV in these patients. We report the results of a mutational analysis study in patients with isolated complex IV deficiency screened for mutations in all structural genes as well as assembly genes known to cause complex IV deficiency. Four patients carried mutations in the complex IV assembly gene SURF1. One patient harbored a mutation in the COX10 gene involved in heme A synthesis. Mutations in the 10 nuclear encoded structural genes were not present.
Coenen
Marieke J H
MJ
Department of Paediatrics, Nijmegen Centre for Mitochondrial Disorders, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, the Netherlands.
Smeitink
Jan A M
JA
Pots
Jeanette M
JM
van Kaauwen
Edwin
E
Trijbels
Frans J M
FJ
Hol
Frans A
FA
van den Heuvel
Lambert P
LP
D019883:Alkyl and Aryl Transferases / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D015331:Cohort Studies; D030401:Cytochrome-c Oxidase Deficiency / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D018832:Molecular Chaperones; D009154:Mutation / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D017421:Sequence Analysis
D002352:Carrier Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; C489345:SCO1 protein, human; C400285:SCO2 protein, human; C092928:Surf-1 protein; C490115:COX10 protein, human; D003576:Electron Transport Complex IV; D019883:Alkyl and Aryl Transferases