Mitochondrial DNA mutations in cardiomyopathy: Combination of replacements yielding cysteine residues and tRNA mutations

✍ Scribed by Masashi Tanaka; Toshihiro Obayashi; Makoto Yoneda; Sergey A. Kovalenko; Satoru Sugiyama; Takayuki Ozawa

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 497 KB
• Volume: 18
• Category: Article
• ISSN: 0148-639X
• DOI: 10.1002/mus.880181432

✦ Synopsis

Mutations occur in mitochondrial DNA (mtDNA) in a strand-asymmetric manner. The suppressed usage of cysteine residues in the H-strandencoded 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 lipidperoxidation products, and this gain, possibly in association with tRNA mutations, can be a genetic risk factor for degenerative diseases. o