Hypersensitivity to oxygen
and shortened lifespan in a Drosophila mitochondrial complex II mutant
D.
W. Walker, P. Hajek, J. Muffat, D.
Knoepfle, S. Cornelison, G.
Attardi, and S. Benzer
Proceedings of the National Academy of Sciences
103
16382-16387
(2006)
doi:10.1073/PNAS.0607918103
Oxidative stress is implicated as a major cause of aging and age-related
diseases, such as Parkinson's and Alzheimer's, as well as ischemia-reperfusion injury in stroke.
The mitochondrial electron transport chain is the principal source of reactive oxygen species
within cells. Despite considerable medical interest, the molecular mechanisms that regulate
reactive oxygen species formation within the mitochondrion remain poorly understood. Here, we
report the isolation and characterization of a Drosophila mutant with a defect in subunit b of
succinate dehydrogenase (SDH; mitochondrial complex II). The sdhB mutant is hypersensitive to
oxygen and displays hallmarks of a progeroid syndrome, including early-onset mortality and
age-related behavioral decay. Pathological analysis of the flight muscle, which is amongst the
most highly energetic tissues in the animal kingdom, reveals structural abnormalities in the
mitochondria. Biochemical analysis shows that, in the mutant, there is a complex II-specific
respiratory defect and impaired complex II-mediated electron transport, although the other
respiratory complexes remain functionally intact. The complex II defect is associated with an
increased level of mitochondrial hydrogen peroxide production, suggesting a possible mechanism
for the observed sensitivity to elevated oxygen concentration and the decreased lifespan of the
mutant fly.