The interorganellar interaction between distinct human mitochondria with deletion mutant mtDNA from a patient with mitochondrial disease and with HeLa mtDNA

For the examination of possible intermitochondrial interaction of human mitochondria from different cells, cybrids were constructed by introducing HeLa mitochondria into cells with respiration-deficient (rho(-)) mitochondria, Respiration deficiency was due to the predominance of mutant mtDNA with a 5,196-base pair deletion including five tRNA genes (Delta mtDNA(5196)). The HeLa mtDNA and Delta mtDNA(5196) encoded chloramphenicol-resistant (CAP(r)) and chloramphenicol-sensitive (CAPS) 16 S rRNA, respectively. The first evidence for the interaction was that polypeptides exclusively encoded by Delta mtDNA(5196) were translated on the introduction of HeLa mitochondria, suggesting supplementation of the missing tRNAs by rho(-) mitochondria from HeLa mitochondria. Second, the exchange of mitochondrial rRNAs was observed; even in the presence of CAP, CAP(s) Delta mtDNA(5196)-specific polypeptides as well as those encoded by CAP(r) HeLa mtDNA were translated in the cybrids, These phenomena can be explained assuming that the translation in rho(-) mitochondria was restored by tRNAs and CAP(r) 16 S rRNA supplied from HeLa mitochondria, unambiguously indicating interorganellar interaction, These observations introduce a new concept of the dynamics of the mitochondrial genetic system and help in understanding the relationship among mtDNA mutations and expression of human mitochondrial diseases and aging.