title: Mitochondrial DNA mutations in cardiomyopathy: combination of replacements yielding cysteine residues and tRNA mutations.
abstract: Mutations occur in mitochondrial DNA (mtDNA) in a strand-asymmetric manner. The suppressed usage of cysteine residues in the H-strand-encoded subunits can be ascribed to the mutational instability of the codon for cysteine. The usage of cysteine was suppressed even in the L-strand-encoded ND6 subunit in which the codon for cysteine was stable. Survey of the entire sequences of mtDNA from 43 individuals revealed three amino acid replacements creating cysteine residues. A patient with fatal infantile cardiomyopathy carried a mutation causing a Tyr-->Cys replacement along with three tRNA mutations. A patient with hypertrophic cardiomyopathy carried two mutations causing a Ser-->Cys replacement and a Tyr-->Cys replacement besides two tRNA mutations. The gain of cysteine residues might accelerate the inactivation of the subunits either by reactive oxygen species or by lipid-peroxidation products, and this gain, possibly in association with tRNA mutations, can be a genetic risk factor for degenerative diseases.
authors.affiliation: Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Obayashi
authors.forename: M
authors.initials: M
authors.lastname: Yoneda
authors.forename: S A
authors.initials: SA
authors.lastname: Kovalenko
authors.forename: S
authors.initials: S
authors.lastname: Sugiyama
authors.forename: T
authors.initials: T
authors.lastname: Ozawa
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D009202:Cardiomyopathies / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics; D003062:Codon; D003545:Cysteine / Q000235:genetics* / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D012343:RNA, Transfer / Q000235:genetics*
chemical_list: D003062:Codon; D004272:DNA, Mitochondrial; D012343:RNA, Transfer; D003545:Cysteine