A mutation in a mitochondrial dehydrogenase/reductase gene causes an increased sensitivity to oxidative stress and mitochondrial defects in the nematode Caenorhabditis elegans

rad-8 is an interesting mutant that shows increased sensitivities to UV radiation and reactive oxygen species in the nematode Caenorhabditis elegans. In this study, we have characterized rad-8 and have found that rad-8 showed several phenotypes of mitochondrial dysfunction such as a decreased activity of the respiratory chain, increased generation of superoxide anions, increased oxidative damage, increased apoptosis, and abnormal mitochondrial structure. Our genetic analysis has also indicated that rad-8 has a causative mutation in the F56H1.6 gene, which encodes a mitochondrial dehydrogenase/reductase. The functional role of RAD-8 may be evolutionarily conserved because expression of the putative human homologue RTIWIP/NIMP in rad-8 rescued the increased sensitivity to oxygen in rad-8. These results suggest that RAD-8 plays an important role in oxygen metabolism in mitochondria in higher eukaryotes.