NAD Metabolism and Regulation: Lessons From Yeast.

Nicotinamide adenine dinucleotide (NAD) is an essential metabolite involved in various cellular processes. The cellular NAD pool is maintained by three biosynthesis pathways, which are largely conserved from bacteria to human. NAD metabolism is an emerging therapeutic target for several human disorders including diabetes, cancer, and neuron degeneration. Factors regulating NAD homeostasis have remained incompletely understood due to the dynamic nature and complexity of NAD metabolism. Recent studies using the genetically tractable budding yeast have identified novel NAD homeostasis factors. These findings help provide a molecular basis for how may NAD and NAD homeostasis factors contribute to the maintenance and regulation of cellular function. Here we summarize major NAD biosynthesis pathways, selected cellular processes that closely connect with and contribute to NAD homeostasis, and regulation of NAD metabolism by nutrient-sensing signaling pathways. We also extend the discussions to include possible implications of NAD homeostasis factors in human disorders. Understanding the cross-regulation and interconnections of NAD precursors and associated cellular pathways will help elucidate the mechanisms of the complex regulation of NAD homeostasis. These studies may also contribute to the development of effective NAD-based therapeutic strategies specific for different types of NAD deficiency related disorders.