title: Repression of the mitochondrial peroxiredoxin antioxidant system does not shorten life span but causes reduced fitness in Caenorhabditis elegans.
abstract: The mitochondrial free radical theory of aging proposes that aging is a consequence of progressive mitochondrial dysfunction caused by lifelong accumulation of oxidative damage. Aging is therefore expected to accelerate if the rate of this oxidative damage accumulation increases. Studies attempting to test this prediction through modulation of oxidative damage by altering antioxidant defenses have reported conflicting results. Here we investigated the effects of repressing prdx-3, responsible for the detoxification of mitochondrial hydrogen peroxide, in developmentally normal wild-type Caenorhabditis elegans. We report that life span and levels of oxidative protein damage were not altered when prdx-3 was repressed in adult nematodes. We further found evidence that mitochondrial uncoupling increased in response to repression of prdx-3. Nevertheless repression of prdx-3 led to reductions in steady-state levels of ATP, motility, and brood size, indicating the importance of this enzyme to normal life in C. elegans.
authors.affiliation: Department of Biochemistry, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Manickaratnam
authors.initials: M
authors.lastname: Ranjan
authors.forename: Jan
authors.initials: J
authors.lastname: Gruber
authors.forename: Li Fang
authors.initials: LF
authors.lastname: Ng
authors.forename: Barry
authors.initials: B
authors.lastname: Halliwell
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D005609:Free Radicals / Q000378:metabolism; D056084:Genetic Fitness / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000008:administration & dosage* / Q000378:metabolism; D008136:Longevity / Q000187:drug effects / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress; D061105:Peroxiredoxin III / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D061105:Peroxiredoxin III; D013482:Superoxide Dismutase
keywords: C. elegans; DCFDA; ETC; Mitochondria; Peroxiredoxin-3; ROS; Reactive oxygen species; UCP-4; dichlorofluorescein diacetate; electron transport chain; peroxiredoxin 3; prdx-3; reactive oxygen species; sod-2; superoxide dismutase 2; uncoupling protein 4