The
mev-1(
kn1) mutant of C. elegans is hypersensitive to oxygen. Unlike the wild type, its lifespan dramatically decreased as oxygen concentration was increased. Recently, we have shown that
mev-1 encodes a subunit of the enzyme succinate dehydrogenase cytochrome b (Cyt-1), which is a component of complex II of the mitochondrial electron transport chain [Nature 394:694(1998)]. We have also reported that the ability of complex II to catalyze electron transport from succinate to ubiquinone is compromised in
mev-1 animals. To further elucidate the effects of the
mev-1 mutation, we examined the expression of
cyt-1 in wild type and
mev-1 mutants using a number of different experimental approaches. Histological methods were employed to show that, in young adults, succinate dehydrogenase activity was clearly present in wild type but was undetectable in
mev-1 animals. Using Western and Northern analyses,
cyt-1 expression was found to be similar in
mev-1 and wild type, with relatively constant amounts of mRNA but increasing amounts of protein accumulating throughout development. Transmission electron microscopy revealed that
mev-1 mitochondria had morphological abnormalities, particularly at high (50%) oxygen concentrations. In young adults, these included the presence of electron-dense inclusions and disorganized cristae. In embryos,
mev-1 nuclei had an appearance characteristic of those undergoing chromosome fragmentation. These EM data are consistent with Nomarski DIC microscopy, which showed that the number of apoptotic cells was significantly higher in
mev-1 than in wild-type embryos. Elevated apoptosis was suppressed by
ced-3 , indicating that the abnormal signal in
mev-1 embryos triggered the normal
ced-3 /
ced-9 apoptotic pathway. Unlike with wild type, many
mev-1 embryos failed to hatch when subjected to high oxygen concentrations. Taken together, these data indicate that Cyt-1 plays a key role in the regulation not only in aging but throughout development of C. elegans . In addition, the data reveal new pathological manifestations of the
mev-1 mutation.