A Stop-Codon Mutation in the Human mtDNA Cytochrome c Oxidase I Gene Disrupts the Functional Structure of Complex IV

摘要: Summary We have identified a novel stop-codon mutation in the mtDNA of young woman with multisystem mitochondrial disorder. Histochemical analysis muscle-biopsy sample showed virtually absent cytochrome c oxidase (COX) stain, and biochemical studies confirmed an isolated reduction COX activity. Sequence mitochondrial-encoded COX-subunit genes heteroplasmic G→A transition at nucleotide position 6930 gene for subunit I (COX I). The changes glycine codon to stop codon, resulting predicted loss last 170 amino acids (33%) polypeptide. was present patient's muscle, myoblasts, blood not detected normal or disease controls. It from leukocytes mother, sister, four maternal aunts. studied genetic, biochemical, morphological characteristics transmitochondrial cybrid cell lines, obtained by fusing platelets patient human cells lacking endogenous (ρ 0 cells). There direct relationship between proportion mutant defect. also observed that threshold phenotypic expression this lower than reported mutations involving tRNA genes. suggest G6930A causes disruption assembly respiratory-chain complex IV.