Institute of Immunology, University Medical Center, Hamburg, Germany.
FEBS Lett. 2011 Jun 6;585(11):1651-6. doi: 10.1016/j.febslet.2011.03.045. Epub 2011 Mar 31.
NAD(+) plays central roles in energy metabolism as redox carrier. Recent research has identified important signalling functions of NAD(+) that involve its consumption. Although NAD(+) is synthesized mainly in the cytosol, nucleus and mitochondria, it has been detected also in vesicular and extracellular compartments. Three protein families that consume NAD(+) in signalling reactions have been characterized on a molecular level: ADP-ribosyltransferases (ARTs), Sirtuins (SIRTs), and NAD(+) glycohydrolases (NADases). Members of these families serve important regulatory functions in various cellular compartments, e.g., by linking the cellular energy state to gene expression in the nucleus, by regulating nitrogen metabolism in mitochondria, and by sensing tissue damage in the extracellular compartment. Distinct NAD(+) pools may be crucial for these processes. Here, we review the current knowledge about the compartmentation and biochemistry of NAD(+)-converting enzymes that control NAD(+) signalling.
NAD(+) 在能量代谢中作为氧化还原载体发挥核心作用。最近的研究确定了 NAD(+) 的重要信号功能,涉及 NAD(+) 的消耗。尽管 NAD(+) 主要在细胞质、细胞核和线粒体中合成,但也在囊泡和细胞外隔室中检测到。已经在分子水平上表征了三种在信号反应中消耗 NAD(+) 的蛋白家族:ADP-核糖基转移酶 (ARTs)、Sirtuins (SIRTs) 和 NAD(+) 糖基水解酶 (NADases)。这些家族的成员在各种细胞隔室中发挥重要的调节功能,例如,通过将细胞能量状态与细胞核中的基因表达联系起来,通过调节线粒体中的氮代谢,以及通过感知细胞外隔室中的组织损伤。不同的 NAD(+) 池可能对这些过程至关重要。在这里,我们回顾了关于控制 NAD(+) 信号的 NAD(+) 转化酶的区室化和生物化学的最新知识。