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.
Liu
Chun-Yi
CY
Institute of Biochemistry and Molecular Biology, School of Life Science, National Yang-Ming University, Taipei 112, Taiwan.
Lee
Cheng-Feng
CF
Wei
Yau-Huei
YH
D017209:Apoptosis / Q000528:radiation effects*; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D045304:Cytochromes c / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics*; D004789:Enzyme Activation / Q000528:radiation effects; D017353:Gene Deletion; D006801:Humans; D006822:Hybrid Cells / Q000528:radiation effects*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D017246:Ophthalmoplegia, Chronic Progressive External / Q000235:genetics; D014466:Ultraviolet Rays
D061945:Caspase Inhibitors; D004272:DNA, Mitochondrial; D009842:Oligopeptides; C403753:benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone; C403754:benzyloxycarbonyl-leucyl-glutamyl-histidyl-aspartic acid fluoromethyl ketone; D045304:Cytochromes c; D053148:Caspase 3