Fig. 1. Regulation of NAD⁺ steady-state concentrations.

Free intracellular NAD⁺ pools are regulated predominantly by biosynthetic (green) and consumption (blue) pathways, which synthesize or turn over NAD⁺ molecules, respectively. In mammalian cells, NAD⁺ synthesis largely depends on the salvage pathway. Thus, the specific targeting of the mammalian salvage pathway through inhibition of NAMPT results in robust depletion of NAD⁺ abundance in the subcellular compartments tested here because resident consuming mechanisms are left intact. QaPRT, quinolinate phosphoribosyltransferase; NaMN, nicotinic acid mononucleotide; NMNAT, nicotinamide mononucleotide adenylyltransferase; NaAD, nicotinic acid adenine dinucleotide; NR, nicotinamide riboside; NMN, nicotinamide mononucleotide; NRK, nicotinamide riboside kinase; Nam, nicotinamide.