Heteroplasmic mitochondrial tRNA(Lys) mutation and its complementation in MERRF patient-derived mitochondrial transformants.

The heteroplasmic tRNA(Lys) mutation in the mitochondrial DNA (mtDNA) is responsible for the phenotypic expression and the transmission of MERRF syndrome. However, the genetic behaviors of the mutant and wild-type mtDNA molecules within a cell are still unknown. We demonstrated a clear genetic complementation of the mutant and wild-type mtDNAs, with a sharp threshold around 10% in the wild-type, in the MERRF transformants, and in their subclones by a cytoplast transfer of the mitochondria into an mtDNA-less cell line, rho o cell. By contrast, no interaction was observed between the two functionally complementary mtDNAs that were originally located in distinct organelles and sequentially introduced into a rho o cell line (genetic independence). These results imply that the sorting of the mtDNA molecules among mitochondria plays a crucial role in the phenotypic expression and transmission of the disease.