Cytoplasmic genetics of mammalian cells: conditional sensitivity to mitochondrial inhibitors and isolation of new mutant phenotypes.
We report here that glucose, as a carbon source, and pyruvate are required for the phenotypic expression of cytoplasmically transmitted chloramphenicol-resistance (CAP-R) mutations, recovery of CAP-R mutants, and continuous growth in the presence of oligomycin or antimycin. We assume that glucose supplies additional energy when mitochondrial respiration is diminished and that pyruvate provides intermediates when the Krebs cycle is inhibited. Thus, the requirement for pyruvate is fully satisfied by an exogenous source of purines, and partially by alpha-ketoglutarate or a pyrimidine source. Based upon these findings, we have obtained two types of mutations affecting mitochondrial function--oligomycin resistance and pyruvate-independent expression of chloramphenicol resistance. Both are cytoplasmically transmitted and provide new markers for a genetic analysis of mitochondrial biogenesis.
D000818:Animals; D002460:Cell Line; D002701:Chloramphenicol / Q000494:pharmacology*; D003470:Culture Media; D004272:DNA, Mitochondrial / Q000235:genetics*; D004351:Drug Resistance; D005819:Genetic Markers; D005947:Glucose / Q000494:pharmacology; D007668:Kidney; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010641:Phenotype; D011773:Pyruvates / Q000494:pharmacology
D003470:Culture Media; D004272:DNA, Mitochondrial; D005819:Genetic Markers; D011773:Pyruvates; D002701:Chloramphenicol; D005947:Glucose