The P(174)L mutation in the human hSCO1 gene affects the assembly of cytochrome c oxidase

Biochem Biophys Res Commun. 2000 Dec 20;279(2):341-7. doi: 10.1006/bbrc.2000.3949.


Mutations of the yeast SCO1 gene result in impaired COX assembly. Recently, heterozygous mutations in the human homologue hSCO1 have been reported in infants suffering from neonatal ketoacidotic coma and isolated COX deficiency (Valnot et al., 2000). One of the hSCO1 alleles harboured a frame shift mutation resulting in a premature stop codon, the other a missense mutation leading to a substitution of proline(174) by leucine. This position is next to the essential CXXXC motif, which is conserved in all Sco1p homologues. We used chimeric proteins with the amino-terminal portion derived from yeast Sco1p and carboxy-terminal portion including the CXXXC motif from the human hSco1p to provide experimental evidence for the pathogenic nature of the P(174)L mutation. These chimeras are able to complement yeast sco1 null mutants. Introduction of the P(174)L mutation affects the function of these chimeric proteins severely, as shown by impaired COX assembly and loss of COX activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • DNA Primers
  • Electron Transport Complex IV / genetics
  • Electron Transport Complex IV / metabolism*
  • Genetic Complementation Test
  • Heterozygote
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mitochondria / enzymology
  • Mitochondrial Proteins
  • Mutation, Missense*
  • Promoter Regions, Genetic
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins*


  • DNA Primers
  • Membrane Proteins
  • Mitochondrial Proteins
  • Recombinant Fusion Proteins
  • SCO1 protein, S cerevisiae
  • SCO1 protein, human
  • Saccharomyces cerevisiae Proteins
  • Electron Transport Complex IV