An oligomycin-resistant variant of human fibrosarcoma HT1080 was isolated and characterized as nuclear and codominant. The mutant was stable, was not cross-resistant to respiratory inhibitors, and it contained a mitochondrial ATPase which was less sensitive to oligomycin. Hybrids formed between the human mutant and a mouse cell line expressed the resistance phenotype. By a detailed karyotypic analysis of these hybrids using trypsin-Giemsa banding it was found that resistance to oligomycin correlated with the retention of two human chromosomes 10. The hybrid lines contained only mouse mitochondrial DNA as shown by analyses of mitochondrially synthesized proteins and mitochondrial DNA. The study assigns an ATPase oligomycin-resistance locus to human chromosome 10 and suggests that mouse and human subunits can combine in a functional enzyme complex.
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