Introducing a novel human mtDNA mutation into the Paracoccus denitrificans COX I gene explains functional deficits in a patient.
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Lucioli S, Hoffmeier K, Carrozzo R, Tessa A, Ludwig B, Santorelli FM
Introducing a novel human mtDNA mutation into the Paracoccus denitrificans COX I gene explains functional deficits in a patient.
Neurogenetics. 2006 Mar;7(1):51-7. Epub 2005 Nov 12.
- PubMed ID
- 16284789 [ View in PubMed]
- 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 a3. 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.