Mitochondrial genetics of mammalian cells: a mouse antimycin-resistant mutant with a probable alteration of cytochrome b.
Mouse LA9 antimycin-resistant mutants (ANT-R) were isolated and characterized. Genetic analyses established that this phenotype is encoded within the mtDNA: (1) the ANT-R phenotype showed frequent mitotic segregation and reassortment in hybrid clonal lines; (2) it was transmitted directly in cybrid crosses; and (3) it was cotransmitted in cybrid crosses with the mitochondrial CAP-R marker. Furthermore, the genetic studies suggested that the LA9 CAP-R ANT-R cells were heteroplasmic and contained at least two mtDNA genotypes, cap-r ant-s and cap-s ant-r. Cellular respiration of the ANT-R mutant was markedly more resistant to inhibition by antimycin than that of the parental ANT-S cells. The increased resistance of cellular respiration was entirely accounted for by an increase in the resistance of mitochondrial succinate-cytochrome c oxidoreductase to antimycin inhibition. There was no detectable change in the specific activity of the oxidoreductase in mitochondria of resistant ANT-R cells nor in the sensitivity of the complex to three other specific inhibitors of the complex: TTFA, myxothiazol, and HQNO. Taken together, these studies indicate that the ANT-R phenotype is most likely encoded within the mitochondrial cytochrome b gene and, more specifically, within an antimycin binding domain.
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology*; D002459:Cell Fusion; D003573:Cytochrome b Group / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D004351:Drug Resistance; D006822:Hybrid Cells / Q000502:physiology; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency; D007739:L Cells / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000201:enzymology; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics*; D010101:Oxygen Consumption / Q000187:drug effects; D013384:Succinate Cytochrome c Oxidoreductase / Q000235:genetics*; D013937:Thymidine Kinase / Q000172:deficiency
D003573:Cytochrome b Group; D004272:DNA, Mitochondrial; D000968:Antimycin A; D010088:Oxidoreductases; D013384:Succinate Cytochrome c Oxidoreductase; D007041:Hypoxanthine Phosphoribosyltransferase; D013937:Thymidine Kinase