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.