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Characterization of Nuclear Sirtuins: Molecular Mechanisms and Physiological Relevance

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Histone Deacetylases: the Biology and Clinical Implication

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 206))

Abstract

Sirtuins are protein deacetylases/mono-ADP-ribosyltransferases found in organisms ranging from bacteria to humans. This group of enzymes relies on nicotinamide adenine dinucleotide (NAD+) as a cofactor linking their activity to the cellular metabolic status. Originally found in yeast, Sir2 was discovered as a silencing factor and has been shown to mediate the effects of calorie restriction on lifespan extension. In mammals seven homologs (SIRT1−7) exist which evolved to have specific biological outcomes depending on the particular cellular context, their interacting proteins, and the genomic loci to where they are actively targeted. Sirtuins biological roles are highlighted in the early lethal phenotypes observed in the deficient murine models. In this chapter, we summarize current concepts on non-metabolic functions for sirtuins, depicting this broad family from yeast to mammals.

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Acknowledgments

We thank Lei Zhong, Jean Pierre Etchegaray, Magali Silberman, Barbara Martinez, and Agustina D’Urso for helpful discussions and critically reading this manuscript. Carlos Sebastian is the recipient of a Beatriu de Pinos Postdoctoral Fellowship (Generalitat de Catalunya), and Debra Toiber is the recipient of the Brain Power for Israel Fellowship. Work in Mostoslavsky’s laboratory is funded by grants from NIH and MLSC. Raul Mostoslavsky is a Sidney Kimmel Scholar and the recipient of an AFAR award.

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    Debra Toiber, Carlos Sebastian & Raul Mostoslavsky

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  1. Debra Toiber
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Correspondence to Raul Mostoslavsky .

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  1. , Department of Pharmacology, Duke University, Durham, 27710, North Carolina, USA

    Tso-Pang Yao

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    Edward Seto

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Toiber, D., Sebastian, C., Mostoslavsky, R. (2011). Characterization of Nuclear Sirtuins: Molecular Mechanisms and Physiological Relevance. In: Yao, TP., Seto, E. (eds) Histone Deacetylases: the Biology and Clinical Implication. Handbook of Experimental Pharmacology, vol 206. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-21631-2_9

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