Studies of COX16, COX19, and PET191 in human cytochrome-c oxidase deficiency.
BACKGROUND
Cytochrome-c oxidase (COX) is the terminal enzyme of the mitochondrial electron transport chain, and COX deficiency is a common cause of mitochondrial diseases. Cytochrome-c oxidase is composed of 13 subunits, of which 3 are encoded by mitochondrial DNA and 10 by nuclear DNA. Mutations have been identified in each of the 3 mitochondrial DNA genes but in none of the nuclear DNA genes. However, COX deficiency has been attributed to mutations in several nuclear DNA-encoded ancillary proteins needed for COX assembly and function. Despite this progress, the molecular basis of COX deficiency remains elusive in many patients, justifying the identification and screening of additional COX assembly genes, such as COX16, COX19, and PET191.


OBJECTIVE
To determine if COX16, COX19, and PET191 are implicated in human COX deficiency.


METHODS
Mutation screening was performed on 53 patients with isolated COX deficiency by direct sequencing of COX19 and by single-strand conformational polymorphism analysis for COX16 and PET191.


RESULTS
No mutations were found in COX16, COX19, or PET191 in these patients.


CONCLUSIONS
The COX16, COX19, and PET191 genes are either not involved or very rarely involved in human COX deficiency. Mutations in additional COX assembly genes remain to be identified.
Tay
Stacey K H
SK
Departments of Neurology, Genetics and Development, and Pathology, Columbia University College of Physicians and Surgeons, 630 W. 168th Street, New York, NY 10032, USA.
Nesti
Claudia
C
Mancuso
Michelangelo
M
Schon
Eric A
EA
Shanske
Sara
S
Bonilla
Eduardo
E
Davidson
Mercy M
MM
Dimauro
Salvatore
S
D002648:Child; D030401:Cytochrome-c Oxidase Deficiency / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D021122:Protein Subunits / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
C472291:COX16 protein, S cerevisiae; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins