MITOCHONDRIAL-DNA MUTATIONS IN CARDIOMYOPATHY - COMBINATION OF REPLACEMENTS YIELDING CYSTEINE RESIDUES AND TRANSFER-RNA MUTATIONS

Mutations occur in mitochondrial DNA (mtDNA) in a strand-asymmetric ma nner. The suppressed usage of cysteine residues in the H-strand-encode d subunits can be ascribed to the mutational instability of the codon for cysteine. The usage of cysteine was suppressed even in the L-stran d-encoded ND6 subunit in which the codon for cysteine was stable. Surv ey of the entire sequences of mtDNA from 43 individuals revealed three amino acid replacements creating cysteine residues. A patient with fa tal infantile cardiomyopathy carried a mutation causing a Tyr-->Cys re placement 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 cy steine residues might accelerate the inactivation of the subunits eith er by reactive oxygen species or by lipid-peroxidation products, and t his gain, possibly in association with tRNA mutations, can be a geneti c risk factor for degenerative diseases. (C) 1995 John Wiley and Sons, Inc.