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 Saccharomyces cerevisiae 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.