Yeast Control NAD+ Levels by Regulating Nicotinamide Riboside and Nicotinic Acid Export: Preclinical Findings

Synopsis

NAD+ serves as both a key coenzyme in metabolic reactions and a substrate for enzymes like sirtuins that regulate aging and stress responses. Its synthesis is essential for extending lifespan in yeast and depends on precursors such as tryptophan, nicotinic acid, nicotinamide, and nicotinamide riboside. Supplementing cells with these precursors raises NAD+ levels and promotes longevity. This study revealed that nicotinamide riboside and nicotinic acid act not only as vitamins but also as exported metabolites. When the transporter for nicotinamide riboside (Nrt1) was deleted, yeast cells released more of it, allowing the researchers to engineer a strain that produced high amounts of extracellular nicotinamide riboside. They also found that nicotinamide is converted outside the cell into nicotinic acid through an intracellular enzyme, and that deleting the nicotinic acid transporter (Tna1) increased its export as well. These findings show that yeast cells tightly control NAD+ metabolism by regulating both the uptake and release of its vitamin precursors, highlighting an important extracellular dimension to NAD+ balance.

Journal

PLoS ONE