The genetics of the mitochondrial DNA of mammalian somatic cells, their hybrids and cybrids.

A brief review is attempted of the status of the genetics of the mitochondria of mammalian cells in vitro. Reverse segregant human-mouse hybrid strains are unusually stable and retain mitochondrial DNA (mtDNA) of both species for many generations but eventually lose the mtDNA of the species whose chromosomes are segregated. A molecular interchange resembling recombination among mtDNA molecules can be detected in these hybrids. Eisenstadt and co-workers have shown that chloramphenicol inhibits protein synthesis less in mitochondria isolated form chloramphenicol-resistant, mutant cell strains than from sensitive strains. They have also shown that resistance is effectively transmitted by cytoplast fusion. These genetic markers are, therefore, probably in the mtDNA of mammals as they are in yeast. Although chloramphenicol resistance has not been transferred from one distinct species to another by cytoplast fusion, we find that different subspecies of mouse are able to exchange resistance. We have also transferred chloramphenicol resistance to ("transformed") 10(-3) sensitive cells by treating them with purified mtDNA from resistant cells. Treatment with DNA from Escherichia coli and/or mtDNA purified from sensitive cells does not transform. Treatment with nuclear DNA, however, from either sensitive or resistant cells does transform. We suggest that exogenously applied nuclear DNA acts as a potent mutagen in mitochondria. A potential application of the mtDNA transformation phenomenon to molecular cloning of DNA in mammalian mitochondria is proposed.