Department of Microbiology and Molecular Genetics, College of Biological Sciences, University of California, One Shields Ave., Davis, CA, 95616, USA.
Curr Genet. 2019 Oct;65(5):1113-1119. doi: 10.1007/s00294-019-00972-0. Epub 2019 Apr 16.
NAD (nicotinamide adenine dinucleotide) is an essential metabolite involved in a myriad of cellular processes. The NAD pool is maintained by three biosynthesis pathways, which are largely conserved from bacteria to human with some species-specific differences. Studying the regulation of NAD metabolism has been difficult due to the dynamic flexibility of NAD intermediates, the redundancy of biosynthesis pathways, and the complex interconnections among them. The budding yeast Saccharomyces cerevisiae provides an efficient genetic model for the isolation and study of factors that regulate specific NAD biosynthesis pathways. A recent study has uncovered a putative cross-regulation between the de novo NAD biosynthesis and copper homeostasis mediated by a copper-sensing transcription factor Mac1. Mac1 appears to work with the Hst1-Sum1-Rfm1 complex to repress the expression of de novo NAD biosynthesis genes. Here, we extend the discussions to include additional nutrient- and stress-sensing pathways that have been associated with the regulation of NAD homeostasis. NAD metabolism is an emerging therapeutic target for several human diseases. NAD preservation also helps ameliorate age-associated metabolic disorders. Recent findings in yeast contribute to the understanding of the molecular basis underlying the cross-regulation of NAD metabolism and other signaling pathways.
烟酰胺腺嘌呤二核苷酸（NAD）是一种参与多种细胞过程的必需代谢物。NAD 池由三种生物合成途径维持，这些途径从细菌到人类基本保持保守，但存在一些种属特异性差异。由于 NAD 中间产物的动态灵活性、生物合成途径的冗余性以及它们之间的复杂相互联系，研究 NAD 代谢的调节一直很困难。 budding 酵母 Saccharomyces cerevisiae 为分离和研究调节特定 NAD 生物合成途径的因素提供了有效的遗传模型。最近的一项研究揭示了从头合成 NAD 生物合成和铜稳态之间的一种假定的交叉调节，这种调节由一个铜感应转录因子 Mac1 介导。Mac1 似乎与 Hst1-Sum1-Rfm1 复合物一起工作，以抑制从头合成 NAD 生物合成基因的表达。在这里，我们将讨论扩展到包括与 NAD 动态平衡调节相关的其他营养和应激感应途径。NAD 代谢是几种人类疾病的新兴治疗靶点。NAD 的保存还有助于改善与年龄相关的代谢紊乱。酵母中的最新发现有助于理解 NAD 代谢和其他信号通路交叉调节的分子基础。
