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Mitochondrial DNA mutations in cardiomyopathy: Combination of replacements yielding cysteine residues and tRNA mutations
Author(s) -
Tanaka Masashi,
Obayashi Toshihiro,
Yoneda Makoto,
Kovalenko Sergey A.,
Sugiyama Satoru,
Ozawa Takayuki
Publication year - 1995
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.880181432
Subject(s) - mitochondrial dna , transfer rna , mutation , cardiomyopathy , cysteine , genetics , dna , mitochondrion , biology , biochemistry , microbiology and biotechnology , chemistry , gene , medicine , rna , heart failure , enzyme
Abstract 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 lipid‐peroxidation products, and this gain, possibly in association with tRNA mutations, can be a genetic risk factor for degenerative diseases. © 1995 John Wiley & Sons, Inc.