title: Origin, cellular expression, and cybrid transmission of mitochondrial CAP-R, PYR-IND, and OLI-R mutant phenotypes.
abstract: Chloramphenicol-resistant (CAP-R) mouse and Chinese hamster lines were isolated in a single selection step in drug medium containing pyruvate. Cellular expression of the CAP-R phenotype required pyruvate--or an appropriate substitute--as a nutritional supplement. Subclone lines which were pyruvate independent (PYR-IND) arose in second-step selections at a high frequency. CAP-R PYR-IND Chinese hamster mutants could be directly isolated in single-step selections but at a very low frequency. Subclone lines (OLI-R) which were cross-resistant to oligomycin were isolated in a third selection cycle. The PYR-IND and OLI-R phenotypes were cotransmitted with the CAP-R mtDNA mutation but were expressed at the cellular level only if the number of mutant mitochondrial genomes exceeded a minimum threshold value. Analysis of a mtDNA restriction fragment alteration in one series of mutants supported this model. Threshold limits for cellular expression of mitochondrial mutant phenotypes are likely to be a general phenomenon and will constrain models of the origin and segregation of mtDNA mutations.
mesh_terms: D000818:Animals; D002460:Cell Line; D002701:Chloramphenicol / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D004272:DNA, Mitochondrial / Q000235:genetics*; D004351:Drug Resistance; D005796:Genes; D006822:Hybrid Cells / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D009840:Oligomycins / Q000494:pharmacology; D010641:Phenotype; D011773:Pyruvates / Q000494:pharmacology; D019289:Pyruvic Acid
chemical_list: D004272:DNA, Mitochondrial; D009840:Oligomycins; D011773:Pyruvates; D002701:Chloramphenicol; D019289:Pyruvic Acid