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首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >Long-lived Indy induces reduced mitochondrial reactive oxygen species production and oxidative damage
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Long-lived Indy induces reduced mitochondrial reactive oxygen species production and oxidative damage

机译：长寿印地诱导线粒体活性氧的产生减少和氧化损伤

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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.
机译：Indy活性降低会延长D. melanogaster的寿命，而繁殖力，代谢率或运动能力不会显着降低。为了了解导致此突变株寿命延长的潜在机制，我们比较了成年Indy突变株的头部和胸部的全基因组基因表达变化与对照蝇在其寿命过程中的变化。代谢和信号通路的特征富集分析表明，从第20天开始，Indy的氧化磷酸化途径中的基因表达水平显着降低。我们通过实验证实，电子传递链的复合物I和III在Indy中的酶活性较低。蝇在第20天之前存活，并预测线粒体中活性氧（ROS）的产生会减少。一致地，我们发现在印地方面，相对于对照而言，ROS的产生和蛋白质的损伤均减少了。但是，我们没有发现总ATP的显着差异，该表型可以通过我们在Indy突变体中发现更高的线粒体密度来解释。因此，Indy突变体延长寿命的一种潜在机制可能是通过改变线粒体生理，从而提高了ATP / ROS的效率。

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