Lifespan extension by calorie restriction relies on the Sty1 MAP kinase stress pathway
Lifespan extension by calorie restriction relies on the Sty1 MAP kinase stress pathway
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DOI：
10.1038/emboj.2009.407
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发表时间：
2010-03-03
期刊：
影响因子：
11.4
通讯作者：
Hidalgo, Elena
中科院分区：
文献类型：
--
作者：
Zuin, Alice;Carmona, Merce;Hidalgo, Elena
无论是热量限制，营养依赖的PKA或TOR/SCH9途径的功能丧失，还是应激防御的激活，都可以提高不同真核生物的寿命。然而，葡萄糖耗竭、营养依赖途径和应激反应之间的分子联系尚不清楚。在这里，我们表明，无论是热量限制还是营养依赖途径的失活都会导致分裂酵母寿命的延长，而且这种影响依赖于压力依赖的丝裂原激活蛋白(MAP)激酶的激活。在葡萄糖限制条件下，Sty1被激活并触发转录应激程序，而在富糖条件下，这种激活不会发生。SCH9-同源物、Sck 2或Pka1激酶编码基因的缺失，或者导致Sty1应激途径结构性激活的突变，都会在富糖条件下延长寿命，重要的是，这种有益的影响最终取决于Sty1。此外，缺乏Pka1的细胞在富糖条件下表现出更高的氧耗量和Sty1的激活。我们得出结论，卡路里限制有利于氧化代谢、活性氧的产生和Sty1蛋白激酶的激活，这一应激途径有利于延长寿命。EMBO期刊(2010)29,981-991。DOI：10.1038/Intemj.2009.407；2010年1月14日在线发布
Either calorie restriction, loss-of-function of the nutrient-dependent PKA or TOR/SCH9 pathways, or activation of stress defences improves longevity in different eukaryotes. However, the molecular links between glucose depletion, nutrient-dependent pathways and stress responses are unknown. Here, we show that either calorie restriction or inactivation of nutrient-dependent pathways induces lifespan extension in fission yeast, and that such effect is dependent on the activation of the stress-dependent Sty1 mitogen-activated protein (MAP) kinase. During transition to stationary phase in glucose-limiting conditions, Sty1 becomes activated and triggers a transcriptional stress programme, whereas such activation does not occur under glucose-rich conditions. Deletion of the genes coding for the SCH9-homologue, Sck2 or the Pka1 kinases, or mutations leading to constitutive activation of the Sty1 stress pathway increase lifespan under glucose-rich conditions, and importantly such beneficial effects depend ultimately on Sty1. Furthermore, cells lacking Pka1 display enhanced oxygen consumption and Sty1 activation under glucose-rich conditions. We conclude that calorie restriction favours oxidative metabolism, reactive oxygen species production and Sty1 MAP kinase activation, and this stress pathway favours lifespan extension. The EMBO Journal (2010) 29, 981-991. doi: 10.1038/emboj.2009.407; Published online 14 January 2010