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    題名: Long-lived Indy induces reduced mitochondrial reactive oxygen species production and oxidative damage
    作者: Neretti, Nicola;Wang, Pei-Yu;Brodsky, Alexander S.;Nyguyen, Hieu H.;White, Kevin P.;Rogina, Blanka;Helfand, Stephen L.
    Wang, Pei-Yu
    貢獻者: 神科所
    關鍵詞: electron transport chain;mitochondria;oxidative phosphorylation;Drosophila;aging
    日期: 2009-02
    上傳時間: 2018-11-21 16:23:04 (UTC+8)
    摘要: Decreased Indy activity extends lifespan in D. melanogaster without significant reduction in fecundity, metabolic rate, or locomotion. To understand the underlying mechanisms leading to lifespan extension in this mutant strain, we compared the genome-wide gene expression changes in the head and thorax of adult Indy mutant with control flies over the course of their lifespan. A signature enrichment analysis of metabolic and signaling pathways revealed that expression levels of genes in the oxidative phosphorylation pathway are significantly lower in Indy starting at day 20. We confirmed experimentally that complexes I and III of the electron transport chain have lower enzyme activity in Indy long-lived flies by Day 20 and predicted that reactive oxygen species (ROS) production in mitochondria could be reduced. Consistently, we found that both ROS production and protein damage are reduced in Indy with respect to control. However, we did not detect significant differences in total ATP, a phenotype that could be explained by our finding of a higher mitochondrial density in Indy mutants. Thus, one potential mechanism by which Indy mutants extend life span could be through an alteration in mitochondrial physiology leading to an increased efficiency in the ATP/ROS ratio.
    關聯: Proceedings of the National Academy of Sciences of the United States of America, Vol.106, No.7, pp.2277-2282
    PMID: 19164521
    資料類型: article
    DOI 連結: https://doi.org/10.1073/pnas.0812484106
    DOI: 10.1073/pnas.0812484106
    顯示於類別:[神經科學研究所 ] 期刊論文


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