Zid Brian M, Rogers Aric N, Katewa Subhash D, Vargas Misha A, Kolipinski Marysia C, Lu Tony Au, Benzer Seymour, Kapahi Pankaj
California Institute of Technology, Pasadena, CA 91125, USA.
Cell. 2009 Oct 2;139(1):149-60. doi: 10.1016/j.cell.2009.07.034.
Dietary restriction (DR) extends lifespan in multiple species. To examine the mechanisms of lifespan extension upon DR, we assayed genome-wide translational changes in Drosophila. A number of nuclear encoded mitochondrial genes, including those in Complex I and IV of the electron transport chain, showed increased ribosomal loading and enhanced overall activity upon DR. We found that various mitochondrial genes possessed shorter and less structured 5'UTRs, which were important for their enhanced mRNA translation. The translational repressor 4E-BP, the eukaryotic translation initiation factor 4E binding protein, was upregulated upon DR and mediated DR dependent changes in mitochondrial activity and lifespan extension. Inhibition of individual mitochondrial subunits from Complex I and IV diminished the lifespan extension obtained upon DR, reflecting the importance of enhanced mitochondrial function during DR. Our results imply that translational regulation of nuclear-encoded mitochondrial gene expression by 4E-BP plays an important role in lifespan extension upon DR. For a video summary of this article, see the PaperFlick file with the Supplemental Data available online.
饮食限制（DR）可延长多种物种的寿命。为了研究DR延长寿命的机制，我们检测了果蝇全基因组的翻译变化。许多核编码的线粒体基因，包括电子传递链复合体I和IV中的基因，在DR作用下显示核糖体负载增加且整体活性增强。我们发现各种线粒体基因拥有更短且结构更少的5'非翻译区（5'UTR），这对其增强的mRNA翻译很重要。翻译抑制因子4E-BP，即真核翻译起始因子4E结合蛋白，在DR作用下上调，并介导了DR依赖的线粒体活性变化和寿命延长。抑制复合体I和IV中的单个线粒体亚基会减少DR所带来的寿命延长，这反映了DR期间线粒体功能增强的重要性。我们的结果表明，4E-BP对核编码线粒体基因表达的翻译调控在DR延长寿命中起重要作用。有关本文的视频总结，请参阅在线提供的补充数据中的PaperFlick文件。
