Extended Data Fig. 10: Proposed model of how NAD+ regulates pyrimidines.
From: NAD+ regulates nucleotide metabolism and genomic DNA replication
a, Pathways that maintain mitochondrial NAD(H) levels and metabolic activity. Oaa, oxaloacetate; α-KG, α-ketoglutarate; Succ, succinate; Fum, fumarate; Mal, malate; I-V, electron transport chain complexes. Illustration made with BioRender. b-d, Temporal effects of NAD+ treatment. During non-treated conditions, mitochondrial metabolic activity sustains ATP production and pyrimidine synthesis for DNA replication (b). Short-term treatment with NAD+ boosts cellular metabolism, nucleotide synthesis and DNA replication (c). Extended NAD+ treatment results in increased mitochondrial membrane potential, impaired pyrimidine biosynthesis, and depletion of pyrimidines for DNA replication (d). Gln, glutamine; Oligom, oligomycin.
