Increased mitochondrial biogenesis preserves intestinal stem cell homeostasis and contributes to longevity in Indy mutant flies.
Increased mitochondrial biogenesis preserves intestinal stem cell homeostasis and contributes to longevity in Indy mutant flies.
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DOI：
10.18632/aging.100658
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发表时间：
2014-04
期刊：
影响因子：
--
通讯作者：
Rogina B
中科院分区：
文献类型：
--
作者：
Rogers RP;Rogina B
果蝇Indy（I'm Not Dead Yet）基因编码Krebs循环中间体的质膜转运蛋白，在与代谢相关的组织中具有稳健表达。减少INDY以类似于热量限制（CR）的方式改变代谢并延长寿命;然而，对INDY减少的组织特异性生理效应知之甚少。在这里，我们集中在果蝇中肠的INDY减少的影响，由于肠道组织的稳态在健康衰老和长寿的重要性。中肠中Indy mRNA的表达随着衰老和营养而变化。Indy表达的遗传减少增加了线粒体调节因子spargel/dPGC-1的中肠表达，这伴随着线粒体生物发生增加和活性氧（ROS）减少。Indy突变中肠的这些生理变化保持了肠干细胞（ISC）的稳态，并与健康衰老有关。遗传学研究证实，dPGC-1介导的调节作用的INDY，如缺乏寿命延长和ISC稳态的果蝇与突变的Indy和dPGC 1。我们的数据表明，INDY可能是一种生理调节剂，通过调节dPGC-1来调节中间代谢，以响应营养可用性和生物体需求的变化
The Drosophila Indy (I'm Not Dead Yet) gene encodes a plasma membrane transporter of Krebs cycle intermediates, with robust expression in tissues associated with metabolism. Reduced INDY alters metabolism and extends longevity in a manner similar to caloric restriction (CR); however, little is known about the tissue specific physiological effects of INDY reduction. Here we focused on the effects of INDY reduction in the Drosophila midgut due to the importance of intestinal tissue homeostasis in healthy aging and longevity. The expression of Indy mRNA in the midgut changes in response to aging and nutrition. Genetic reduction of Indy expression increases midgut expression of the mitochondrial regulator spargel/dPGC-1, which is accompanied by increased mitochondrial biogenesis and reduced reactive oxygen species (ROS). These physiological changes in the Indy mutant midgut preserve intestinal stem cell (ISC) homeostasis and are associated with healthy aging. Genetic studies confirm that dPGC-1 mediates the regulatory effects of INDY, as illustrated by lack of longevity extension and ISC homeostasis in flies with mutations in both Indy and dPGC1. Our data suggest INDY may be a physiological regulator that modulates intermediary metabolism in response to changes in nutrient availability and organismal needs by modulating dPGC-1
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