C6ORF66 is an assembly factor of mitochondrial complex I

Am J Hum Genet. 2008 Jan;82(1):32-8. doi: 10.1016/j.ajhg.2007.08.003.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calmodulin-Binding Proteins / genetics*
  • Calmodulin-Binding Proteins / metabolism*
  • Child
  • Child, Preschool
  • Consanguinity
  • Electron Transport Complex I / chemistry
  • Electron Transport Complex I / metabolism*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Mutation, Missense
  • Pedigree


  • Calmodulin-Binding Proteins
  • Mitochondrial Proteins
  • NDUFAF4 protein, human
  • Electron Transport Complex I