YCL047C/POF1 is a Novel Nicotinamide Mononucleotide Adenylyltransferase (NMNAT) in Saccharomyces cerevisiae [Microbiology]

April 25th, 2014 by Kato, M., Lin, S.-J.

Nicotinamide adenine dinucleotide (NAD+) is an essential metabolic cofactor involved in various cellular biochemical processes. Nicotinamide riboside (NR) is an endogenously produced key pyridine metabolite that plays important roles in the maintenance of NAD+ pool. Using a NR-specific cell-based screen, we identified mutants that exhibit altered NR release phenotype. Yeast cells lacking the ORF YCL047C/POF1 release considerably more NR compared to wild type, suggesting POF1 plays an important role in NR/NAD+ metabolism. The amino acid sequence of Pof1 indicates that it is a putative nicotinamide mononucleoti de adenylyltransferase (NMNAT). Unlike other yeast NMNATs, Pof1 exhibits NMN-specific adenylyltransferase activity. Deletion of POF1 significantly lowers NAD+ levels, decreases the efficiency of NR utilization, resistance to oxidative stress, and NR-induced life span extension. We also show that NR is constantly produced by multiple nucleotidases and that the intracellular NR pools are likely to be compartmentalized, which contribute to the regulation of NAD+ homeostasis. Our findings may contribute to the understanding of the molecular basis and regulation of NAD+ metabolism in higher eukaryotes. Pyridine nucleotides NAD+ H) and regulation of NAD+ metabolism in higher eukaryotes.