The role of sirtuins in cellular homeostasis

Kupis, Wioleta; Pałyga, Jan; Tomal, Ewa; Niewiadomska, Ewa

doi:10.1007/s13105-016-0492-6

Cited by 149 publications

(128 citation statements)

References 67 publications

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“…The tissue concentration of NAD + is determined by the relative balance between consumption and biosynthesis (Figure ). The proteins and pathways involved in the consumption of NAD + have been comprehensively reviewed and are only briefly described here (Figure ). Sirtuin enzymes are NAD + ‐dependent proteins that remove acyl moieties from lysine residues in histones and a wide range of different proteins throughout the cell.…”

Section: Nad+ Homeostasismentioning

confidence: 99%

“…There are seven sirtuin isoforms in mammals (Sirt1‐7), present in different subcellular locations. Reversible acylation is present in numerous cellular pathways and can influence many protein characteristics (eg, subcellular location, enzyme kinetics, protein‐protein interactions) and, as a result, sirtuins have been linked with the regulation of a wide spectrum of cellular functions …”

Section: Nad+ Homeostasismentioning

confidence: 99%

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NAD⁺: A key metabolic regulator with great therapeutic potential

Sultani

Samsudeen

Osborne

et al. 2017

J Neuroendocrinology

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+) is a ubiquitous metabolite that serves an essential role in the catabolism of nutrients. Recently, there has been a surge of interest in NAD + biology, with the recognition that NAD + influences many biological processes beyond metabolism, including transcription, signalling and cell survival.There are a multitude of pathways involved in the synthesis and breakdown of ).This redox cycling of NAD + is a key process across numerous metabolic pathways (eg, glycolysis, oxidative phosphorylation).By contrast to its redox role where the levels of NAD + stay essentially constant, NAD + has more recently gained attention following recognition that it also functions as a co-substrate for a range of different enzymes, including sirtuins, poly(ADP-ribose) polymerases (PARPs) and cyclic ADP-ribose synthases, where NAD + is actively degraded during the enzymatic processes catalysed by these proteins.Because of the breadth of cellular processes regulated by these en- | NAD + HOMEOSTASISThe 11The main pathways involved in the biosynthesis of NAD + are the Preiss-Handler pathway, the de novo biosynthesis pathway and

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Section: Nad+ Homeostasismentioning

confidence: 99%

Section: Nad+ Homeostasismentioning

confidence: 99%

NAD⁺: A key metabolic regulator with great therapeutic potential

Sultani

Samsudeen

Osborne

et al. 2017

J Neuroendocrinology

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“…This protein is also involved in DNA damage repair. In neurons, it plays a role in DSBR (double-strand break Table 1 Localization and function for mammalian sirtuins Adapted from Shoba et al (2009), Houtkooper et al (2012 and Kupis et al (2016) AceCS2 acetyl-CoA synthetase 2, CPS1 carbamoyl phosphate synthetase 1, DNA Polb DNA polymerase b, FOXO forkhead box O, GABPb1 GA-binding protein b1, GDH glutamate dehydrogenase, HIF1a hypoxia-inducible factor 1a, NFjB nuclear factor-jB, PAR3 partitioning defective 3 homologue, PEPCK phosphoenolpyruvate carboxykinase, PGC1a peroxisome proliferator-activated receptor-c-co-activator, SOD2 superoxide dismutase 2, UCP-1 uncoupling protein 1, UOX urate oxidase repair) via NHEJ, while in proliferating cells, SIRT1 is involved in homologous recombination and base excision repair (BER) (Fang et al 2016). Yamamori et al (2010) proved that human AP endonucelase 1 (APE1) is a target for deacetylation by SIRT1, a protein that is directly involved in the repair of damaged DNA.…”

Section: Sirtuins In Animalsmentioning

confidence: 99%

“…SIRT1, SIRT2, SIRT3 belong to class I, SIRT4 to class II, SIRT5 to III and SIRT6 and SIRT7 to class IV (Frye 2000;Houtkooper et al 2012). They differ in cell localization, tissue localization, enzymatic activity, substrates and biological implications (Huang et al 2007;Shoba et al 2009;Houtkooper et al 2012;Whitaker et al 2013;König et al 2014;Kupis et al 2016) (Table 1).…”

Section: Introductionmentioning

confidence: 99%

Sirtuins: not only animal proteins

Szućko

2016

Acta Physiol Plant

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Sirtuins are proteins belonging to the group of NADH-dependent deacetylase and mono-ADP-ribosyltransferase enzymes. Sirtuins have been discovered for the first time in yeasts, subsequent studies have shown their presence in bacteria, plants and animals. These enzymes are frequently called longevity enzymes due to the fact that they are part of genetic apparatus involved in aging control. In animals, sirtuins are key regulators of cell defense in response to stress caused by many metabolic processes; they are also involved in the regulation of cell division, metabolism, gene silencing and genetic material repair as well as apoptosis. Thus far, only several well-known research teams have been studying plant proteins resembling animal sirtuins. Considering the fact how essential functions sirtuins play in other organisms, it is extremely interesting to understand their role in plants, especially that the knowledge about them is still limited. It is believed that the function of sirtuins in Arabidopsis thaliana is associated with mitochondrial energy metabolism. Possibly they may also control the synthesis of auxins or proteins involved in their transport, or they may be responsible for regulating cellular response to auxin action. In rice, sirtuins are necessary for the protection against genomic instability and cell damage that guarantee their growth. They also take part in a defensive response against Pseudomonas syringae. They may also be involved in the ripening of fruits.Moreover, their functions are associated with photosynthetic activity and aging of leaves.

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“…During the last decade, it has become clear that the cellular role of NAD + extends far beyond its classic participation in redox reactions, since it also acts as a substrate of several families of regulatory enzymes [1–4]. For this reason, intracellular concentrations of many NAD + intermediates are maintained low [5–8], and NAD + is considered as a sensor of metabolic and cellular stress [9–11].…”

Section: Introductionmentioning

confidence: 99%

Characterization and mutational analysis of a nicotinamide mononucleotide deamidase from Agrobacterium tumefaciens showing high thermal stability and catalytic efficiency

et al. 2017

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NAD+ has emerged as a crucial element in both bioenergetic and signaling pathways since it acts as a key regulator of cellular and organismal homeostasis. Among the enzymes involved in its recycling, nicotinamide mononucleotide (NMN) deamidase is one of the key players in the bacterial pyridine nucleotide cycle, where it catalyzes the conversion of NMN into nicotinic acid mononucleotide (NaMN), which is later converted to NAD+ in the Preiss-Handler pathway. The biochemical characteristics of bacterial NMN deamidases have been poorly studied, although they have been investigated in some firmicutes, gamma-proteobacteria and actinobacteria. In this study, we present the first characterization of an NMN deamidase from an alphaproteobacterium, Agrobacterium tumefaciens (AtCinA). The enzyme was active over a broad pH range, with an optimum at pH 7.5. Moreover, the enzyme was quite stable at neutral pH, maintaining 55% of its activity after 14 days. Surprisingly, AtCinA showed the highest optimal (80°C) and melting (85°C) temperatures described for an NMN deamidase. The above described characteristics, together with its high catalytic efficiency, make AtCinA a promising biocatalyst for the production of pure NaMN. In addition, six mutants (C32A, S48A, Y58F, Y58A, T105A and R145A) were designed to study their involvement in substrate binding, and two (S31A and K63A) to determine their contribution to the catalysis. However, only four mutants (C32A, S48A Y58F and T105A) showed activity, although with reduced catalytic efficiency. These results, combined with a thermal and structural analysis, reinforce the Ser/Lys catalytic dyad mechanism as the most plausible among those proposed.

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The role of sirtuins in cellular homeostasis

Abstract: Sirtuins are evolutionarily conserved nicotinamide adenine dinucleotide (NAD+)-dependent lysine deacylases or ADP-ribosyltransferases. These cellular enzymes are metabolic sensors sensitive to NAD+ levels that maintain physiological homeostasis in the animal and plant cells.

Cited by 149 publications

References 67 publications

NAD⁺: A key metabolic regulator with great therapeutic potential

NAD⁺: A key metabolic regulator with great therapeutic potential

Sirtuins: not only animal proteins

Characterization and mutational analysis of a nicotinamide mononucleotide deamidase from Agrobacterium tumefaciens showing high thermal stability and catalytic efficiency

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The role of sirtuins in cellular homeostasis

Abstract: Sirtuins are evolutionarily conserved nicotinamide adenine dinucleotide (NAD+)-dependent lysine deacylases or ADP-ribosyltransferases. These cellular enzymes are metabolic sensors sensitive to NAD+ levels that maintain physiological homeostasis in the animal and plant cells.

Cited by 149 publications

References 67 publications

NAD+: A key metabolic regulator with great therapeutic potential

NAD+: A key metabolic regulator with great therapeutic potential

Sirtuins: not only animal proteins

Characterization and mutational analysis of a nicotinamide mononucleotide deamidase from Agrobacterium tumefaciens showing high thermal stability and catalytic efficiency

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Product

Resources

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NAD⁺: A key metabolic regulator with great therapeutic potential

NAD⁺: A key metabolic regulator with great therapeutic potential