The role of sirtuins in cellular homeostasis
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MINI REVIEW
The role of sirtuins in cellular homeostasis Wioleta Kupis & Jan Pałyga & Ewa Tomal & Ewa Niewiadomska
Received: 28 July 2015 / Accepted: 26 April 2016 # The Author(s) 2016. This article is published with open access at Springerlink.com
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. Keywords Deacetylation . Deacylation . Mono-ADPribosylation . Mammalian and plant sirtuins . Sirtuin activators and inhibitors
Introduction Acetylation, catalyzed by acetyltransferases that transfer an acetyl residue from acetyl-CoA to the ε-amino group of specific lysine residues in histones and other proteins, is responsible for chromatin activation and regulation of metabolic pathways. A reverse process, the removal of acetyl group from the lysine of acetylated proteins, requires the participation of enzymes known as lysine deacetylases (KDACs). In general, the lysine deacetylases were divided into four classes: class I, II, W. Kupis : J. Pałyga (*) : E. Tomal Department of Biochemistry and Genetics, Institute of Biology, Jan Kochanowski University, ul. Świętokrzyska 15, 25-406 Kielce, Poland e-mail: [email protected] E. Niewiadomska Institute of Plant Physiology, Polish Academy of Sciences, Niezapominajek 21, 30-239 Kraków, Poland
III, and IV [49]. Since a yeast transcriptional repressor Sir2 (silent information regulator 2) is a founding member in the class III deacetylases, the homologue proteins in other organisms have been named sirtuins. Sirtuins constitute a highly conserved family of deacetylases that depend on the oxidized form of nicotinamide adenine dinucleotide (NAD+) [6]. Seven homologs of yeast Sir2 (SIRT1–7) which share a conserved catalytic domain have been identified in mammals [23]. Sirtuins differ in subcellular localization, enzymatic activity, and targets (Table 1). SIRT1, SIRT6, and SIRT7 are nuclear proteins while SIRT2 is mainly a cytoplasmic protein but it can translocate into nucleus as well [59]. SIRT3, SIRT4, and SIRT5 are mitochondrial sirtuins [50]. Sirtuins play an important role in the regulation of cellular homeostasis, in particular metabolism [30], inflammation [27], oxidative stress [55], and senescence [53]. It is believed that activation of sirtuins may be advantageous not only in metabolic diseases such as type 2 diabetes and obesity, but also in neurodegenerative diseases [17]. This is in part because the sirtuins stimulate the activity of mitochondria, the energy centers of the cells, and mitochondrial proteins, preventing physiological changes underlying many pathological conditions [30].
Structure of sirtuins All sirtuins possess a conserved catalytic NAD+-binding domain, consisting of about 275 amino acids, which is flanked by the N- and C-terminal sequences of variable length [54]. The N- and C-terminal extensions are the
K. Wioleta
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