A systematic RNAi screen identifies a critical role for mitochondria in C-elegans longevity
A systematic RNAi screen identifies a critical role for mitochondria in C-elegans longevity
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DOI：
10.1038/ng1056
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发表时间：
2003-01-01
期刊：
影响因子：
30.8
通讯作者：
Ruvkun, G
中科院分区：
文献类型：
--
作者：
Lee, SS;Lee, RYN;Ruvkun, G
我们报告了一个系统的RNA干扰（RNAi）屏幕的5,690线虫基因的基因失活，增加寿命。我们发现，线粒体功能的重要基因脱颖而出，作为一个主要的基因组影响C。elegans寿命。一项经典的遗传学筛查发现了线粒体亮氨酰-tRNA合成酶基因（lrs-2）的突变，该突变损害了线粒体功能，并与较长的寿命有关。线粒体受损的长寿蠕虫具有较低的ATP含量和耗氧量，但对自由基和其他应激的反应不同。这些数据表明，C.线粒体受损的秀丽线虫不能简单地归因于较低的自由基产生，并表明代谢和寿命的更复杂的耦合。
We report a systematic RNA interference (RNAi) screen of 5,690 Caenorhabditis elegans genes for gene inactivations that increase lifespan. We found that genes important for mitochondrial function stand out as a principal group of genes affecting C. elegans lifespan. A classical genetic screen identified a mutation in the mitochondrial leucyl-tRNA synthetase gene (lrs-2) that impaired mitochondrial function and was associated with longer-lifespan. The long-lived worms with impaired mitochondria had lower ATP content and oxygen consumption, but differential responses to free-radical and other stresses. These data suggest that the longer lifespan of C. elegans with compromised mitochrondria cannot simply be assigned to lower free radical production and suggest a more complex coupling of metabolism and longevity.