Quantitative effect of 4977 bp deletion of mitochondrial DNA on the susceptibility of human cells to UV-induced apoptosis.

In this study, we used a series of human cytoplasmic hybrids (cybrids) harboring different proportions of 4977 bp-deleted mtDNA to investigate the quantitative effect of a pathogenic mutation of mtDNA on apoptosis. We found that the sensitivity of human cells to apoptosis triggered by UV irradiation increases with the proportion of 4977 bp-deleted mtDNA. Moreover, UV-induced activation of caspase 3 was preceded by the activation of caspases 8 and 9. Most importantly, we observed that UV-induced cytochrome c release from mitochondria occurred much earlier and was much more pronounced in the cybrids harboring higher proportions of 4977 bp-deleted mtDNA. We suggest that 4977 bp-deleted mtDNA increases the susceptibility of human cells to UV-induced apoptosis in a quantitative manner through cytochrome c release from mitochondria and caspase 3 activation.