Regulation of yeast sirtuins by NAD(+) metabolism and calorie restriction.
Regulation of yeast sirtuins by NAD(+) metabolism and calorie restriction.
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DOI：
10.1016/j.bbapap.2009.09.030
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发表时间：
2010-08
期刊：
影响因子：
--
通讯作者：
Lin SJ
中科院分区：
文献类型：
--
作者：
Lu SP;Lin SJ
Sir2家族蛋白（sirtuins）是进化保守的NAD+（烟酰胺腺嘌呤二核苷酸）依赖蛋白去乙酰化酶和adp核糖基化酶，已被证明在应激反应、基因转录、细胞代谢和长寿的调控中发挥重要作用。最近的研究也表明sirtuins是热量限制（CR）的下游目标，CR介导CR诱导的有益效果，包括以NAD+依赖的方式延长寿命。CR延长了许多物种的寿命，并已被证明可以改善许多与年龄相关的疾病，如糖尿病和癌症。因此，了解CR的机制以及sirtuins的调控将为这些与年龄相关的代谢疾病的分子基础提供见解。本文主要综述了酿酒酵母（Saccharomyces cerevisiae）中sirtuins和NAD+代谢的研究进展。这些研究揭示了CR信号通路和NAD+生物合成通路中关键的代谢长寿因素，这也可能有助于sirtuin活性的调节。NAD+生物合成途径和CR信号通路的许多组分在酵母和包括人类在内的高等真核生物中是保守的。因此，这些发现将有助于阐明与年龄相关的代谢疾病和人类衰老的潜在机制。
The Sir2 family proteins (sirtuins) are evolutionally conserved NAD+ (nicotinamide adenine dinucleotide)-dependent protein deacetylases and ADP-ribosylases, which have been shown to play important roles in the regulation of stress response, gene transcription, cellular metabolism and longevity. Recent studies have also suggested that sirtuins are downstream targets of calorie restriction (CR), which mediate CR-induced beneficial effects including life span extension in a NAD+-dependent manner. CR extends life span in many species and has been shown to ameliorate many age-associated disorders such as diabetes and cancers. Understanding the mechanisms of CR as well as the regulation of sirtuins will therefore provide insights into the molecular basis of these age-associated metabolic diseases. This review focuses on discussing advances in studies of sirtuins and NAD+ metabolism in genetically tractable model system, the budding yeast Saccharomyces cerevisiae. These studies have unraveled key metabolic longevity factors in the CR signaling and NAD+ biosynthesis pathways, which may also contribute to the regulation of sirtuin activity. Many components of the NAD+ biosynthesis pathway and CR signaling pathway are conserved in yeast and higher eukaryotes including humans. Therefore, these findings will help elucidate the mechanisms underlying age-associated metabolic disease and perhaps human aging.
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