Electron transport is facilitated by four complexes that are bound to the mitochondrial inner membrane. In C. elegans , the mutation
mev-1(
kn1) causes a defect in the cytochrome b large subunit (Cyt-1) of complex II, and mutations in
gas-1 result in a defective 49 kDa iron-sulfur protein subunit of complex I. Both mutations render animals susceptible to oxidative stress. We now present a series of interrelated observations on
mev-1 and
gas-1 . First, the levels of the Reactive Oxygen Species (ROS) superoxide anion are substantially elevated in isolated sub-mitochondrial particles (SMP) from both
mev-1 and
gas-1 mutants, particularly when reared under hyperoxic conditions. Interestingly, superoxide anion levels in intact
gas-1 mitochondria were actually lower than in wild type. Second, the concentration of reduced glutathione (GSH), which is an important antioxidant, is substantially reduced in both
mev-1 and
gas-1 animals. These two phenotypes undoubtedly translate into higher levels of oxidative stress in
mev-1 and
gas-1 mutants. Two manifestations of this burden are as follows: i) as evidenced by microscopic examination of animals exposed to the reagent JC1, inner mitochondrial membrane potentials were significantly lower
mev-1 and
gas-1 animals; and ii) as measured using Western blots, the concentrations of mitochondrially localized
ced-9 gene product were different in wild type versus the two mutants; specifically, CED-9 levels increased as a function of oxygen concentration in N2 but decreased in
mev-1 and
gas-1 . These latter two observations help explain the fact that both
mev-1 and
gas-1 embryos contain significantly more apoptotic cells than wild type. In the case of
mev-1, the abnormal cell death is completely suppressed by inclusion of either loss-of-function
ced-3 or
ced-4 mutations into the genetic background, indicating that supernumerary apoptosis operates via the normal
ced-9/ced-4/ced-3 apoptotic pathway. This epistasis experiment has not yet been conducted with the
gas-1 because the double mutant is very difficult to maintain. Collectively, these data demonstrate that mutations (
mev-1 and
gas-1 ) in different complexes of the electron transport chain have very similar consequences, namely heightened susceptibility to oxidative stress and apoptosis. This underscores the importance of mitochondrially induced oxidative stress in aging.