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 huma n mitochondria from different cells, cybrids were constructed by intro ducing 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 chl oramphenicol-resistant (CAP(r)) and chloramphenicol-sensitive (CAPS) 1 6 S rRNA, respectively. The first evidence for the interaction was tha t polypeptides exclusively encoded by Delta mtDNA(5196) were translate d on the introduction of HeLa mitochondria, suggesting supplementation of the missing tRNAs by rho(-) mitochondria from HeLa mitochondria. S econd, the exchange of mitochondrial rRNAs was observed; even in the p resence 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 f rom HeLa mitochondria, unambiguously indicating interorganellar intera ction, These observations introduce a new concept of the dynamics of t he mitochondrial genetic system and help in understanding the relation ship among mtDNA mutations and expression of human mitochondrial disea ses and aging.