Yeast life span extension by depletion of 60S ribosomal subunits is mediated by Gcn4
Yeast life span extension by depletion of 60S ribosomal subunits is mediated by Gcn4
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DOI：
10.1016/j.cell.2008.02.037
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发表时间：
2008-04-18
期刊：
影响因子：
64.5
通讯作者：
Kaeberlein, Matt
中科院分区：
文献类型：
--
作者：
Steffen, Kristan K.;MacKay, Vivian L.;Kaeberlein, Matt
在几乎每一个研究的有机体中，减少热量摄入可以延长寿命。在酵母中，饮食限制导致的跨度延长被认为是由高度保守的营养响应性靶点雷帕霉素（TOR）、蛋白激酶A（PKA）和Sch9激酶介导的。这些激酶协调调节各种细胞过程，包括应激反应、蛋白质周转、细胞生长和核糖体生物合成。在这里，我们表明，60 S核糖体亚基水平的特定减少减缓酵母衰老。缺失编码60S亚基蛋白质或加工因子的基因或用小分子处理（它们都抑制60S亚基生物合成）均足以显著增加复制寿命。降低60S亚基水平导致寿命延长的一种机制是通过诱导Gcn 4，一种营养响应性转录因子。遗传上位性分析表明，饮食限制，减少60 S亚基丰度，和GCN 4激活延长酵母寿命通过类似的机制。
In nearly every organism studied, reduced caloric intake extends life span. In yeast, span extension from dietary restriction is thought to be mediated by the highly conserved, nutrient-responsive target of rapamycin (TOR), protein kinase A (PKA), and Sch9 kinases. These kinases coordinately regulate various cellular processes including stress responses, protein turnover, cell growth, and ribosome biogenesis. Here we show that a specific reduction of 60S ribosomal subunit levels slows aging in yeast. Deletion of genes encoding 60S subunit proteins or processing factors or treatment with a small molecule, which all inhibit 60S subunit biogenesis, are each sufficient to significantly increase replicative life span. One mechanism by which reduced 60S subunit levels leads to life span extension is through induction of Gcn4, a nutrient-responsive transcription factor. Genetic epistasis analyses suggest that dietary restriction, reduced 60S subunit abundance, and Gcn4 activation extend yeast life span by similar mechanisms.