PEROXIDE PRODUCTION AND APOPTOSIS IN CULTURED-CELLS CARRYING MTDNA MUTATION CAUSING ENCEPHALOMYOPATHY

When cybrids with a point mutation, which locates in the tRNA(Leu(UUR) ) gene of mtDNA and causes a mitochondrial encephalomyopathy (MELAS sy ndrome), were exposed to a high concentration of oxygen (95%), the per oxide production markedly increased by 6 h of oxygen exposure, whereas the peroxide production was similar among the cybrids under a normal concentration of oxygen. The peroxide production by oxygen exposure wa s enhanced particularly in cybrids with high proportions of the mutant mtDNA and low respiratory capacities. The appearance of apoptotic cel ls by oxygen exposure was high in cybrids with the impaired respirator y function due to the mutation. An antioxidant NAC successfully suppre ssed both the peroxide production and apoptosis. These results imply t hat the peroxide production plays an important role in inducing apopto sis in :ells carrying; the mtDNA mutation causing encephalomyopathy.