4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila.
4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila.
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DOI：
10.1016/j.cell.2009.07.034
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发表时间：
2009-10-02
期刊：
影响因子：
64.5
通讯作者：
Kapahi P
中科院分区：
文献类型：
--
作者：
Zid BM;Rogers AN;Katewa SD;Vargas MA;Kolipinski MC;Lu TA;Benzer S;Kapahi P
饮食限制（DR）延长了许多物种的寿命。为了研究DR延长寿命的机制，我们分析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和复合体IV中的基因，在dr时显示出核糖体负载增加和总体活性增强。我们发现各种线粒体基因具有更短和更少结构的5 ' utr，这对它们增强mRNA翻译很重要。翻译抑制因子4E- bp，真核翻译起始因子4E结合蛋白，在DR和介导的线粒体活性和寿命延长的DR依赖性变化中上调。抑制复合体I和IV的单个线粒体亚基减少了DR后获得的寿命延长，反映了DR期间线粒体功能增强的重要性。我们的研究结果表明，4E-BP对线粒体基因表达的翻译调节在DR后的寿命延长中起重要作用。
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 implicate translational regulation of mitochondrial gene expression by 4E-BP which plays an important role in lifespan extension upon DR.
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DOI：
10.1083/jcb.115.4.887
发表时间：
1991-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kozak M
通讯作者：
Kozak M
影响因子：
7.8
作者：
Hansen, Malene;Taubert, Stefan;Kenyon, Cynthia
通讯作者：
Kenyon, Cynthia
影响因子：
2.1
作者：
CHIPPINDALE, AK;LEROI, AM;ROSE, MR
通讯作者：
ROSE, MR
影响因子：
9.2
作者：
Kapahi, P;Zid, BM;Benzer, S
通讯作者：
Benzer, S
影响因子：
3.8
作者：
Katewa, Subhash D.;Ballard, J. William O.
通讯作者：
Ballard, J. William O.