FIGURE 2.

Extracellular NAD⁺ derivatives supporting mitochondrial NAD⁺ generation and cell survival. Nam utilization was inhibited by FK866 addition, as indicated. Tryptophan is insufficient as NAD⁺ precursor to maintain cell viability (supplemental Fig. S1A). NA supports mitochondrial NAD⁺ synthesis in 293mitoPARP cells (supplemental Fig. S1B). “NAD precursor” designates the metabolite added to the medium. A, both NAMN and NMN support mitochondrial NAD⁺ formation. NAMN and NMN protect 293mitoPARP cells (B) and HeLa S3 cells (C) from cell death induced by NamPRT inhibition (FK866). D and E, mononucleotide precursors, but not NA, support generation of mitochondrial NAD⁺ and viability of HepG2 cells. Bar, 10 μm. NAD⁺ and NAAD support mitochondrial NAD⁺ (F) formation and cell viability (G) of 293mitoPARP cells.