Figure 6 Cross-compartmental junctions in cellular NAD+ metabolism Figure 6 | Cross-compartmental junctions in cellular NAD+ metabolism. In the nucleus, NAM and NMN are likely to be transported into the mitochondrial and nuclear compartments from the cytosol. Specific NMNAT isoforms and NAMPT are required in each compartment for the salvage of NAD+; however, the presence of NAMPT in the mitochondria is unconfirmed. In addition to the import of reducing equivalents of NADH by the malate–aspartate and glyceraldehyde 3-phosphate shuttles, the TCA cycle also contributes to the overall level of mitochondrial NADH. The reducing power of NADH is then used to make ATP by the electron transport chain, producing NAD+ and ATP. Pathways that need further validation indicated by dashed lines. Abbreviations: ETC, electron transport chain; G3P, glucose-3-phosphatase; M/A, malate–aspartate; NAD+, nicotinamide adenine dinucleotide; NAM, nicotinamide; NAMPT, nicontinamide phosphoribosyltransferase; NMN, NAM mononucleotide; NMNAT, nicotinamide mononucleotide adenylyl transferase; NR, nicotinamide riboside; NRK, nicotinamide riboside kinase; PARP, poly ADP-ribose (PAR) polymerase; TCA, tricarboxylic acid. Menzies, K. J. et al. (2015) Protein acetylation in metabolism—metabolites and cofactors Nat. Rev. Endocrinol. doi:10.1038/nrendo.2015.181