title: Introducing a novel human mtDNA mutation into the Paracoccus denitrificans COX I gene explains functional deficits in a patient.
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.
authors.affiliation: Molecular Medicine, IRCCS, Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Lucioli
authors.forename: Klaus
authors.initials: K
authors.lastname: Hoffmeier
authors.forename: Rosalba
authors.initials: R
authors.lastname: Carrozzo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tessa
authors.forename: Bernd
authors.initials: B
authors.lastname: Ludwig
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
mesh_terms: D000328:Adult; D000818:Animals; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000737:chemistry / Q000235:genetics*; D005260:Female; D006801:Humans; D009154:Mutation; D010231:Paracoccus denitrificans / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D021122:Protein Subunits; D003576:Electron Transport Complex IV