Introducing a novel human mtDNA mutation into the Paracoccus denitrificans COX I gene explains functional deficits in a patient

Simona Lucioli, Klaus Hoffmeier, Rosalba Carrozzo, Alessandra Tessa, Bernd Ludwig, Filippo M. Santorelli

Research output: Contribution to journalArticlepeer-review

Abstract

We identified a novel mutation (S142F) in the human mtDNA CO I gene in a patient with a clinical phenotype resembling mitochondrial cardioencephalomyopathy. To substantiate pathogenicity, we modeled the identified mutation in the homologous gene in Paracoccus denitrificans and analyzed the biochemical consequences. We observed a deleterious effect on enzyme activity, with a lack of heme a 3. Taking advantage of the extensive structural homology between the bacterial enzyme and the mammalian core complex, we conclude that the novel S142F mutation is disease-related. This approach can be used in other cases to support the pathogenicity of novel variants in the mitochondrial genome.

Original languageEnglish
Pages (from-to)51-57
Number of pages7
JournalNeurogenetics
Volume7
Issue number1
DOIs
Publication statusPublished - Mar 2006

Keywords

  • Bacterial model
  • Cytochrome c oxidase
  • MELAS
  • mtDNA mutation
  • Paracoccus denitrificans

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuroscience(all)

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