RNA Interference-Mediated Silencing of Sod2 in Drosophila Leads to Early Adult-Onset Mortality and Elevated Endogenous Oxidative Stress

• Published in: Proceedings of the National Academy of Sciences - PNAS 2002-12, Vol.99 (25), p.16162-16167
• Main Authors: Kirby, Kim, Hu, Jianguo, Hilliker, Arthur J., Phillips, John P.
• Format: Article
• Language: English
• Subjects: Adult insects; Aging; Animals; Biological Sciences; Citric Acid Cycle - genetics; DNA-Binding Proteins; Drosophila; Drosophila melanogaster - enzymology; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - deficiency; Drosophila Proteins - genetics; Drosophila Proteins - physiology; Drug Resistance - genetics; Electron Transport - genetics; Embryos; Enzymes; Genetics; Genotypes; Insect larvae; Insects; Iron-Sulfur Proteins - deficiency; Isoenzymes - deficiency; Isoenzymes - genetics; Isoenzymes - physiology; Larval development; Longevity - genetics; Mitochondria - enzymology; Mortality; Oxidation; Oxidative stress; Oxidative Stress - genetics; Paraquat - toxicity; Promoter Regions, Genetic; Pupae; Reactive Oxygen Species - metabolism; Ribonucleic acid; RNA; RNA Interference; Saccharomyces cerevisiae Proteins - genetics; Superoxide Dismutase - deficiency; Superoxide Dismutase - genetics; Superoxide Dismutase - physiology; Transcription Factors - genetics; Transgenes
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.252342899

Oxidative stress has been widely implicated as an important factor in the aging process. Because mitochondrial respiration is the principal source of reactive oxygen within cells, the mitochondrially localized superoxide dismutase (SOD) 2 is thought to play an important front-line defensive role against aging-related oxidative stress. Although genetic studies with mutants deficient in SOD1, the predominantly cytosolic isoform of SOD, have been instrumental in elucidating the role of reactive oxygen metabolism in aging in Drosophila, the lack of available mutations in the Sod2 gene has hampered an equivalent analysis of the participation of this important antioxidant enzyme in the Drosophila aging model. Here we report that ablation of mitochondrial SOD2 through expression of a GAL4-regulated, inverted-repeat Sod2 RNA-interference transgene in an otherwise normal animal causes increased endogenous oxidative stress, resulting in loss of essential enzymatic components of the mitochondrial respiratory chain and the tricarboxylic acid cycle, enhances sensitivity to applied oxidative stress, and causes early-onset mortality in young adults. In sharp contrast, ablation of SOD2 has no overt effect on the development of larvae and pupae, which may reflect a fundamental transition in oxygen utilization and/or reactive oxygen metabolism that occurs during metamorphosis from larval to adult life.