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 language | English (US) |
|---|---|
| Pages (from-to) | 14271-14281 |
| Number of pages | 11 |
| Journal | Journal of Biological Chemistry |
| Volume | 286 |
| Issue number | 16 |
| DOIs | |
| State | Published - Apr 22 2011 |
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ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
Cite this
Phosphate-responsive signaling pathway is a novel component of NAD + metabolism in saccharomyces cerevisiae. / Lu, Shu Ping; Lin, Su Ju.
In: Journal of Biological Chemistry, Vol. 286, No. 16, 22.04.2011, p. 14271-14281.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phosphate-responsive signaling pathway is a novel component of NAD + metabolism in saccharomyces cerevisiae
AU - Lu, Shu Ping
AU - Lin, Su Ju
PY - 2011/4/22
Y1 - 2011/4/22
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M110.217885
DO - 10.1074/jbc.M110.217885
M3 - Article
VL - 286
SP - 14271
EP - 14281
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 16
ER -