title: C6ORF66 is an assembly factor of mitochondrial complex I.
abstract: Homozygosity mapping was performed in five patients from a consanguineous family who presented with infantile mitochondrial encephalomyopathy attributed to isolated NADH:ubiquinone oxidoreductase (complex I) deficiency. This resulted in the identification of a missense mutation in a conserved residue of the C6ORF66 gene, which encodes a 20.2 kDa mitochondrial protein. The mutation was also detected in a patient who presented with antenatal cardiomyopathy. In muscle of two patients, the levels of the C6ORF66 protein and of the fully assembled complex I were markedly reduced. Transfection of the patients' fibroblasts with wild-type C6ORF66 cDNA restored complex I activity. These data suggest that C6ORF66 is an assembly factor of complex I. Interestingly, the C6ORF66 gene product was previously shown to promote breast cancer cell invasiveness.
authors.affiliation: Metabolic Disease Unit and, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
authors.forename: Ann
authors.initials: A
authors.lastname: Saada
authors.forename: Simon
authors.initials: S
authors.lastname: Edvardson
authors.forename: Matan
authors.initials: M
authors.lastname: Rapoport
authors.forename: Avraham
authors.initials: A
authors.lastname: Shaag
authors.forename: Khaled
authors.initials: K
authors.lastname: Amry
authors.forename: Chaya
authors.initials: C
authors.lastname: Miller
authors.forename: Haya
authors.initials: H
authors.lastname: Lorberboum-Galski
authors.forename: Orly
authors.initials: O
authors.lastname: Elpeleg
mesh_terms: D002148:Calmodulin-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D042967:Electron Transport Complex I / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D028361:Mitochondrial Diseases / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: D002148:Calmodulin-Binding Proteins; D024101:Mitochondrial Proteins; C519296:NDUFAF4 protein, human; D042967:Electron Transport Complex I