Hypersensitivity to oxygen and shortened lifespan in a Drosophila mitochondrial complex II mutant.
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.
Walker
David W
DW
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Hájek
Petr
P
Muffat
Julien
J
Knoepfle
Dan
D
Cornelison
Stephanie
S
Attardi
Giuseppe
G
Benzer
Seymour
S
D000375:Aging / Q000502:physiology*; D000818:Animals; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism* / Q000648:ultrastructure; D004579:Electron Transport; D042963:Electron Transport Complex II / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008854:Microscopy, Electron; D008928:Mitochondria / Q000201:enzymology; D009132:Muscles / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics; D010100:Oxygen / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012119:Respiration
D021122:Protein Subunits; D017382:Reactive Oxygen Species; D042963:Electron Transport Complex II; D010100:Oxygen