Assimilation of Endogenous Nicotinamide Riboside Is Essential for Calorie Restriction-mediated Life Span Extension in Saccharomyces cerevisiae

Lu, Shu Ping; Kato, Michiko; Lin, Su

doi:10.1074/jbc.m109.004010

Cited by 65 publications

(125 citation statements)

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“…Relative NR levels were determined by a liquid-based cross-feeding bioassay (12). To prepare cell extracts for intracellular NR determination, ϳ1.5 ϫ 10 9 (ϳ150 A 600 unit cells) of cells (donors of interest) grown to late logphase (ϳ12 h growth from an A 600 of 0.1) were lysed by bead beating in 800 l of ice-cold 50 mM ammonium acetate solution.…”

Section: Methodsmentioning

confidence: 99%

“…More recently, NR has been shown to be an efficient NAD ϩ precursor that contributes to the NAD ϩ pool and supports NAD ϩ -dependent reactions (9,10). Intact NR salvaging pathway is essential for maintaining NAD ϩ homeostasis and life span (12,13). Because yeast cells constantly release and reassimilate NR, it has been suggested that this NR pool might confer metabolic flexibility for prompt adjustment of cellular NAD ϩ levels (12,13).…”

Section: Pyridine Nucleotides Nadmentioning

confidence: 99%

“…Intact NR salvaging pathway is essential for maintaining NAD ϩ homeostasis and life span (12,13). Because yeast cells constantly release and reassimilate NR, it has been suggested that this NR pool might confer metabolic flexibility for prompt adjustment of cellular NAD ϩ levels (12,13). How NAD ϩ synthesis routes are regulated in response to different growth conditions remains to be elucidated.…”

Section: Pyridine Nucleotides Nadmentioning

confidence: 99%

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YCL047C/POF1 Is a Novel Nicotinamide Mononucleotide Adenylyltransferase (NMNAT) in Saccharomyces cerevisiae

Kato

Lin

2014

Journal of Biological Chemistry

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Section: Methodsmentioning

confidence: 99%

Section: Pyridine Nucleotides Nadmentioning

confidence: 99%

Section: Pyridine Nucleotides Nadmentioning

confidence: 99%

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YCL047C/POF1 Is a Novel Nicotinamide Mononucleotide Adenylyltransferase (NMNAT) in Saccharomyces cerevisiae

Kato

Lin

2014

Journal of Biological Chemistry

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“…However, molecular mechanisms that underlie these beneficial effects remain unclear. (19). To further understand the regulation of NAD + homeostasis, we developed a NR-specific reporter-based bioassay to screen for mutants with altered NR release.…”

mentioning

confidence: 99%

“…To further understand the regulation of NAD + homeostasis, we developed a NR-specific reporter-based bioassay to screen for mutants with altered NR release. This screen system was based on our observations that yeast cells release and transport NR back into the cell (19), a phenomenon that is also conserved in human cells (20). Our studies have identified novel NAD + homeostasis factors including the phosphate responsive signaling (PHO) pathway (17), the SPS amino acid sensing pathway (21), a conserved vacuolar NR transporter Fun26 (1,17) and several NAD + metabolic enzymes (22).…”

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confidence: 99%

A functional link between NAD+ homeostasis and N-terminal protein acetylation in Saccharomyces cerevisiae

Croft¹,

Raj²,

Salemi

et al. 2018

Journal of Biological Chemistry

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(Fig. 1D, upper panel).Similar to pnc1∆ mutant (Fig. 1B), both nat3∆and mdm20∆ released mostly NAM not NA (Fig.1D, lower panel). Fig. 1E (Fig. 2E, top panel) had a lesser effect (Fig. 2E, bottom (Fig. 3B). Next, we tested whether deleting ATG14 was sufficient to restore NAD + levels in the NatB mutants. As shown in Fig. 3C (left panel), deleting ATG14did not rescue the low NAD + levels in nat3∆ cells. Similarly, deleting other factors contributing to NR and NAM production ( Fig. 1A and Fig. 2E) in nat3∆ cells also failed to restore the NAD + level back to wild type ( shown to restore actin cable formation in NatB mutants (23,24,28,29). Interestingly, both TPM1-oe and TPM1-5 largely blocked NA/NAM release in the nat3∆ mutant (Fig. 3D) 1A). N-terminal acetyltransferases have specific targets that are largely determined by the sequence of the first two amino acids. NatB acetylates proteins with a MET-retained residue, followed by ASP, GLU, GLN, or ASN as the second residue (25,26,39,40). Nma1 and Nma2 have a MET-ASP N-terminus, but neither protein has been identified as a NatB target.Similar to nat3∆ mutant, nma1∆ cells showed decreased NAD + levels, which could not be rescued by supplementing NR (Fig. 4B). As for the controls, NR efficiently restored the NAD + level in the npt1∆ mutant, which has functional NR salvage (Fig. 4B). The similarities between nma1∆ and nat3∆ mutants suggested that Nma1and Nma2 activities are likely reduced in nat3∆ cells. Since N-terminal acetylation may affect the turnover of target proteins, we first determined whether reduced Nma1/Nma2 activities were due to decreased Nma1/Nma2 protein levels. As shown in Fig. 4C, Nma1 and Nma2 protein levels were indeed decreased in nat3∆ cells (Fig. 4C). In addition to Nma1 and Nma2, NAD + homeostasis factors Bna2, Bna5and Hst1 are also potential NatB targets. Bna2and Bna5 are biosynthesis enzymes in the de novo pathway (Fig. 1A) DISCUSSIONIn this study we characterized NatB complex as a novel NAD + homeostasis factor.Mutants lacking components of the NatB complex, NAT3 and MDM20, produce and release excess amount of NA and NAM. Our studies showed two pathways downstream of NatB contribute to NAD + homeostasis (Fig. 5).In one, NatB is important for proper NAD + biosynthesis by regulating Nma1/Nma2. NatB mutants have low NAD + levels (Fig. 2C), and all NAD + precursors examined failed to restore the NAD + levels ( Fig. 4A and 4B). This suggests that a NAD + biosynthesis factor(s) required for utilization of all NAD + precursors is defected in NatB mutants. Nma1 and Nma2 are such targets because they are the only factors required for all three NAD + biosynthesis pathways (de novo, NA/NAM salvage, and NR salvage) (Fig. 1A), and the N-terminal amino acid sequences are a match for NatB acetylation. In addition, nma1∆and nat3∆ mutants showed similar NAD + utilization defects (Fig. 4B). Although Nma2 is present in both mutants, Nma2 is known to play a minor role in NAD + metabolism. Supporting this model, decreased Nma1 protein level was observed in t...

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The Nucleobase‐Cation‐Symport‐1 Family of Membrane Transport Proteins

Messerschmidt

Huber²,

Poulos³

et al. 2004

Handbook of Metalloproteins

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The evolutionary relationships of membrane transport proteins of the nucleobase‐cation‐symport (NCS‐1) family from bacteria, fungi, and plants are described. The reported substrates of the NCS‐1 family include nucleobases, hydantoins, and vitamins. Secondary active transport of substrate accompanied by a sodium ion, or possibly a proton, is the usual mechanism of energization. A strategy for the amplified expression, purification, and activity assays of bacterial members of the NCS‐1 family is described. Conditions are given for the production of diffracting crystals of one member, the Na + ‐coupled transporter for aromatic hydantoins, ‘Mhp1’, from Microbacterium liquefaciens . The 3D structures of three forms of the Mhp1 protein are discussed in terms of one open‐outward, one substrate‐occluded, and one open‐inward conformation contributing to a molecular dynamics simulation of the alternating‐access model of membrane transport. The unexpected similarity of the protein fold of Mhp1 to those of transport proteins, hitherto thought to be from different evolutionary families, is discussed.

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Assimilation of Endogenous Nicotinamide Riboside Is Essential for Calorie Restriction-mediated Life Span Extension in Saccharomyces cerevisiae

Cited by 65 publications

References 49 publications

YCL047C/POF1 Is a Novel Nicotinamide Mononucleotide Adenylyltransferase (NMNAT) in Saccharomyces cerevisiae

YCL047C/POF1 Is a Novel Nicotinamide Mononucleotide Adenylyltransferase (NMNAT) in Saccharomyces cerevisiae

A functional link between NAD+ homeostasis and N-terminal protein acetylation in Saccharomyces cerevisiae

The Nucleobase‐Cation‐Symport‐1 Family of Membrane Transport Proteins

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