BEHAVIOR OF A POPULATION OF PARTIALLY DUPLICATED MITOCHONDRIAL-DNA MOLECULES IN CELL-CULTURE - SEGREGATION, MAINTENANCE AND RECOMBINATION DEPENDENT UPON NUCLEAR BACKGROUND

We have studied the dynamics of mitochondrial DNA maintenance and segr egation in human cells using serial cybrid transfer of partially dupli cated mitochondrial DNA, from a mitochondrial myopathy patient, to two distinct recipient cell types. The results indicate two radically dif ferent outcomes dependent upon nuclear background. In one case (lung c arcinoma) there is systematic loss of the partial duplication by an im plied recombinational mechanism. In another nuclear background (osteos arcoma) the duplicated molecules can survive, having only a marginal e ffect on mitochondrial respiratory function. Moreover, in the osteosar coma nuclear background further disturbances of mtDNA maintenance freq uently follow from cybrid transfer. These are progressive, catastrophi c loss of mtDNA and further rearrangement to generate partially tripli cated molecules. The results imply differential expression of nuclear genes regulating mtDNA copy number, replication and recombination in d ifferent human cell types.