The new life of a centenarian: signalling functions of NAD(P)

Berger, Felicitas; Ramírez-Hernández, María Helena; Ziegler, Mathias

doi:10.1016/j.tibs.2004.01.007

Cited by 452 publications

(360 citation statements)

References 70 publications

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“…NAD 1 was detected 100 years ago as a low molecular weight compound necessary for sugar fermentation in yeast extracts (Berger et al, 2004). NAD 1 /NADH and its close analog NADP 1 /NADPH are the soluble carriers of electrons in cells, coupling the oxidation or reduction of a substrate to these electron carriers.…”

Section: Sensing Redox Statusmentioning

confidence: 99%

“…During our introduction to metabolism, we also learn that these molecules can function as allosteric regulators of key enzymes to control pathway flux, reflecting the cellular metabolic state. NAD 1 is also a substrate for poly ADPribose polymerase and the NAD 1 -dependent histone deacetylase (HDAC) during covalent modification of target proteins and also serves as precursor for the calcium mobilizing agents cyclic ADPribose and NADP 1 (Berger et al, 2004). The NAD 1 -dependent HDAC Sir2 gained notoriety when found to function in transcriptional silencing and longevity (Berger et al, 2004).…”

Section: Sensing Redox Statusmentioning

confidence: 99%

“…Additional HDAC substrates are now being uncovered (Berger et al, 2004). It is thought that the NAD 1 dependence of the enzymatic activity of the Sir2 deacetylase provides a sensor for NAD 1 /NADH levels and links the redox state to transcriptional silencing.…”

Section: Sensing Redox Statusmentioning

confidence: 99%

See 2 more Smart Citations

A Renaissance of Metabolite Sensing and Signaling: From Modular Domains to Riboswitches

Templeton

Moorhead

2004

Plant Cell

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Section: Sensing Redox Statusmentioning

confidence: 99%

Section: Sensing Redox Statusmentioning

confidence: 99%

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A Renaissance of Metabolite Sensing and Signaling: From Modular Domains to Riboswitches

Templeton

Moorhead

2004

Plant Cell

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“…NAD and its derivative NADP are crucial metabolites for redox reactions in living organisms and form a basis for almost every metabolic pathway in the cell (Berger et al, 2004;Hunt et al, 2004;Noctor et al, 2006). There is increasing evidence that the biosynthesis, degradation, and recycling of NAD(P)(H) are associated with signal transduction, developmental regulation, and stress resistance (Amor et al, 1998;Imai et al, 2000;North et al, 2003;Mittler et al, 2004;Sánchez et al, 2004;Chai et al, 2005Chai et al, , 2006De Block et al, 2005).…”

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confidence: 99%

Mutation of OsNaPRT1 in the NAD Salvage Pathway Leads to Withered Leaf Tips in Rice

Ren

et al. 2016

Plant Physiol.

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Premature leaf senescence affects plant growth and yield in rice. NAD plays critical roles in cellular redox reactions and remains at a sufficient level in the cell to prevent cell death. Although numerous factors affecting leaf senescence have been identified, few involving NAD biosynthetic pathways have been described for plants. Here, we report the cloning and characterization of Leaf Tip Senescence 1 (LTS1) in rice (Oryza sativa), a recessive mutation in the gene encoding O. sativa nicotinate phosphoribosyltransferase (OsNaPRT1) in the NAD salvage pathway. A point mutation in OsNaPRT1 leads to dwarfism and the withered leaf tip phenotype, and the lts1 mutant displays early leaf senescence compared to the wild type. Leaf nicotinate and nicotinamide contents are elevated in lts1, while NAD levels are reduced. Leaf tissue of lts1 exhibited significant DNA fragmentation and H 2 O 2 accumulation, along with up-regulation of genes associated with senescence. The lts1 mutant also showed reduced expression of SIR2-like genes (OsSRT1 and OsSRT2) and increased acetylation of histone H3K9. Downregulation of OsSRTs induced histone H3K9 acetylation of senescence-related genes. These results suggest that deficiency in the NAD salvage pathway can trigger premature leaf senescence due to transcriptional activation of senescence-related genes.

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“…Therefore efforts to memorize the structures of NAD(P) can be limited to nicotinamide mononucleotide, the other half of these molecules. However, as a result of research over the past 15-20 years a far more complicated picture has emerged also placing NAD(P) + at key positions in cellular signal transduction [1]. Most remarkably, NAD(P) + undergoes structural conversions in these regulatory pathways, including the generation of new molecules [among them, cADPR (cyclic ADP-ribose), O-acetyl ADP-ribose and NAADP (nicotinic acid-adenine dinucleotide phosphate)]; compounds that are not known to participate in any other biochemical pathway.…”

mentioning

confidence: 99%

NAD+ surfaces again

Ziegler

Niere

2004

Biochemical Journal

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NAD + and its metabolites serve important functions in intracellular signalling. NAD + -mediated regulatory processes also take place on the cell surface, particularly of immune cells. In this issue of the Biochemical Journal, Gerth et al. have demonstrated a new mechanism of Ca 2+ uptake into monocytes which is triggered by NAD + or its degradation product, ADP-ribose. These observations point to a hitherto unknown Ca 2+ -influx mechanism and underscore the potential significance of NAD + and ADP-ribose as signalling molecules on the extracellular side of the plasma membrane.Key words: ADP-ribose, calcium, ion transport, immune cell, NAD + , pyridine nucleotide.From most textbooks of biochemistry one may still get the impression that the pyridine nucleotides have been invented just to make our lives a bit easier -they mediate the majority of redox reactions as cofactors (and there are few alternatives). Moreover, pyridine nucleotides contain an AMP moiety, which is also part of ATP. Therefore efforts to memorize the structures of NAD(P) can be limited to nicotinamide mononucleotide, the other half of these molecules. However, as a result of research over the past 15-20 years a far more complicated picture has emerged also placing NAD(P) + at key positions in cellular signal transduction [1]. Most remarkably, NAD(P) + undergoes structural conversions in these regulatory pathways, including the generation of new molecules [among them, cADPR (cyclic ADP-ribose), O-acetyl ADP-ribose and NAADP (nicotinic acid-adenine dinucleotide phosphate)]; compounds that are not known to participate in any other biochemical pathway.So far, most of the NAD + -dependent signalling processes have been shown to contribute to the control of intracellular events. For example, poly-ADP ribosylation takes place primarily in the nucleus and regulates DNA repair, transcription, apoptosis and other fundamental cellular processes. The NAD + -derivative cADPR activates Ca 2+ release from the endoplasmic reticulum and thereby Ca 2+ -dependent pathways. On the other hand, although also present within cells, mono-ADP-ribosylation appears to be largely an extracellular mechanism of NAD + -mediated regulation. All identified ARTs (mono-ADP-ribosyl transferases) of higher eukaryotes are either GPI (glycosylphosphatidylinositol)-anchored or secreted [2,3]. These enzymes transfer the ADPR (ADP-ribose) moiety of NAD + on to acceptor proteins, thereby modulating their biological activities. ARTs are apparently primarily expressed in blood cells and may contribute to immune functions by modifying proteins, for example, of the extracellular matrix [2,3]. Surprisingly, the known mammalian enzymes catalysing the synthesis of cADPR, designated ADP-ribosyl cyclases, are also located on the cell surface (again, primarily of blood cells). This is unexpected inasmuch as the generated messenger, cADPR, has an intracellular function. Despite appreciable efforts, so far no mammalian intracellular ADP-ribosyl cyclase has been characterized at the molecular level. S...

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The new life of a centenarian: signalling functions of NAD(P)

Cited by 452 publications

References 70 publications

A Renaissance of Metabolite Sensing and Signaling: From Modular Domains to Riboswitches

A Renaissance of Metabolite Sensing and Signaling: From Modular Domains to Riboswitches

Mutation of OsNaPRT1 in the NAD Salvage Pathway Leads to Withered Leaf Tips in Rice

NAD+ surfaces again

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