Phosphate-responsive signaling pathway is a novel component of NAD + metabolism in saccharomyces cerevisiae

Shu Ping Lu, Su Ju Lin

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor involved in various cellular biochemical reactions. To date the signaling pathways that regulate NAD+ metabolism remain unclear due to the dynamic nature and complexity of the NAD+ metabolic pathways and the difficulty of determining the levels of the interconvertible pyridine nucleotides. Nicotinamide riboside (NmR) is a key pyridine metabolite that is excreted and re-assimilated by yeast and plays important roles in the maintenance of NAD+ pool. In this study we establish a NmR-specific reporter system and use it to identify yeast mutants with altered NmR/NAD + metabolism. We show that the phosphate-responsive signaling (PHO) pathway contributes to control NAD+ metabolism. Yeast strains with activated PHO pathway show increases in both the release rate and internal concentration of NmR. We further identify Pho8, a PHO-regulated vacuolar phosphatase, as a potential NmR production factor. We also demonstrate that Fun26, a homolog of human ENT (equilibrative nucleoside transporter), localizes to the vacuolar membrane and establishes the size of the vacuolar and cytosolic NmR pools. In addition, the PHO pathway responds to depletion of cellular nicotinic acid mononucleotide (NaMN) and mediates nicotinamide mononucleotide (NMN) catabolism, thereby contributing to both NmR salvage and phosphate acquisition. Therefore, NaMN is a putative molecular link connecting the PHO signaling and NAD+ metabolic pathways. Our findings may contribute to the understanding of the molecular basis and regulation of NAD+ metabolism in higher eukaryotes.

Original languageEnglish (US)
Pages (from-to)14271-14281
Number of pages11
JournalJournal of Biological Chemistry
Volume286
Issue number16
DOIs
StatePublished - Apr 22 2011

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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