CYTOPLASMICALLY INHERITED MUTATIONS OF A HUMAN CELL-LINE RESULTING IN DEFICIENT MITOCHONDRIAL PROTEIN-SYNTHESIS

A large number of mutants deficient in mitochondrial protein synthesis (mtPS-) have been isolated from the human cell line VA2- B by subjecting cells partially depleted of their mtDNA to mutagenic treatments thought to be specific for mtDNA. Each of these mtPS- mutants has less than 10% of the wild- type rate of mitochondrial protein synthesis, exhibits reduced cytochrome oxidase and rutamycin-sensitive ATPase activities, requires high concentrations of glucose, and grows indefinitely in the presence of 100 μg/ml of chloramphenicol (CAP). Fusion of cytoplasts from seven mtPS- mutants to the nucleated thioguanine-resistant VA2-B derivative TG-6 has yielded numerous cybrid clones which grow in CAP plus thioguanine, whereas almost no clones have resulted from the fusion of nucleated mtPS- cells to TG- 6 cells: these results suggest that the gene(s) coding for the phenotype of mtPS- cells is localized in the cytoplasm (mtDNA?). © 1979 Plenum Publishing Corporation.