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Mammalian sirtuins and energy metabolism.

Li X, Kazgan N - Int. J. Biol. Sci. (2011)

Bottom Line: The seven mammalian sirtuins, SIRT1 to SIRT7, have emerged as key metabolic sensors that directly link environmental signals to mammalian metabolic homeostasis and stress response.Recent studies have shed light on the critical roles of sirtuins in mammalian energy metabolism in response to nutrient signals.This review focuses on the involvement of two nuclear sirtuins, SIRT1 and SIRT6, and three mitochondrial sirtuins, SIRT3, SIRT4, and SIRT5, in regulation of diverse metabolic processes.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. lix3@niehs.nih.gov

ABSTRACT
Sirtuins are highly conserved NAD+-dependent protein deacetylases and/or ADP-ribosyltransferases that can extend the lifespan of several lower model organisms including yeast, worms and flies. The seven mammalian sirtuins, SIRT1 to SIRT7, have emerged as key metabolic sensors that directly link environmental signals to mammalian metabolic homeostasis and stress response. Recent studies have shed light on the critical roles of sirtuins in mammalian energy metabolism in response to nutrient signals. This review focuses on the involvement of two nuclear sirtuins, SIRT1 and SIRT6, and three mitochondrial sirtuins, SIRT3, SIRT4, and SIRT5, in regulation of diverse metabolic processes.

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Schematic representation of seven mammalian sirtuins.
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Figure 1: Schematic representation of seven mammalian sirtuins.

Mentions: The seven mammalian sirtuin proteins share a highly conserved NAD+-binding and catalytic core domain, but have distinct flanking N- and C-terminal extensions 12 (Figure 1). Many mammalian sirtuins bears a NAD+-dependant protein deacetylase activity. A variety of acetyl-proteins have been identified as their substrates at different physiological and pathological conditions (Table 1), although whether p53 is a true substrate for SIRT7 is still not clear. The only reported activity of SIRT4, on the other hand, is the NAD+-dependant ADP-ribosyltransferase activity 13, 14. The divergent N and C-termini of sirtuins are responsible for their variation binding partners, substrates, and subcellular localization (9, Figure 1). Three of the mammalian sirtuins, SIRT1, SIRT6, and SIRT7, are nuclear proteins (Figure 1). SIRT1, while predominately a nuclear enzyme, can also shuttle between cytosol and nucleoplasm in various tissues in response to different environmental signals 15. SIRT6 is a nuclear, chromatin-bound protein 16, whereas SIRT7 is highly enriched in nucleolus 17. Three additional mammalian sirtuins, SIRT3, SIRT4, and SIRT5, are found in mitochondria. They participate in a number of metabolic and survival processes associated with the mitochondrial activity (reviewed in 18). The other mammalian sirtuin, SIRT2, is primarily cytosolic.


Mammalian sirtuins and energy metabolism.

Li X, Kazgan N - Int. J. Biol. Sci. (2011)

Schematic representation of seven mammalian sirtuins.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3101526&req=5

Figure 1: Schematic representation of seven mammalian sirtuins.
Mentions: The seven mammalian sirtuin proteins share a highly conserved NAD+-binding and catalytic core domain, but have distinct flanking N- and C-terminal extensions 12 (Figure 1). Many mammalian sirtuins bears a NAD+-dependant protein deacetylase activity. A variety of acetyl-proteins have been identified as their substrates at different physiological and pathological conditions (Table 1), although whether p53 is a true substrate for SIRT7 is still not clear. The only reported activity of SIRT4, on the other hand, is the NAD+-dependant ADP-ribosyltransferase activity 13, 14. The divergent N and C-termini of sirtuins are responsible for their variation binding partners, substrates, and subcellular localization (9, Figure 1). Three of the mammalian sirtuins, SIRT1, SIRT6, and SIRT7, are nuclear proteins (Figure 1). SIRT1, while predominately a nuclear enzyme, can also shuttle between cytosol and nucleoplasm in various tissues in response to different environmental signals 15. SIRT6 is a nuclear, chromatin-bound protein 16, whereas SIRT7 is highly enriched in nucleolus 17. Three additional mammalian sirtuins, SIRT3, SIRT4, and SIRT5, are found in mitochondria. They participate in a number of metabolic and survival processes associated with the mitochondrial activity (reviewed in 18). The other mammalian sirtuin, SIRT2, is primarily cytosolic.

Bottom Line: The seven mammalian sirtuins, SIRT1 to SIRT7, have emerged as key metabolic sensors that directly link environmental signals to mammalian metabolic homeostasis and stress response.Recent studies have shed light on the critical roles of sirtuins in mammalian energy metabolism in response to nutrient signals.This review focuses on the involvement of two nuclear sirtuins, SIRT1 and SIRT6, and three mitochondrial sirtuins, SIRT3, SIRT4, and SIRT5, in regulation of diverse metabolic processes.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. lix3@niehs.nih.gov

ABSTRACT
Sirtuins are highly conserved NAD+-dependent protein deacetylases and/or ADP-ribosyltransferases that can extend the lifespan of several lower model organisms including yeast, worms and flies. The seven mammalian sirtuins, SIRT1 to SIRT7, have emerged as key metabolic sensors that directly link environmental signals to mammalian metabolic homeostasis and stress response. Recent studies have shed light on the critical roles of sirtuins in mammalian energy metabolism in response to nutrient signals. This review focuses on the involvement of two nuclear sirtuins, SIRT1 and SIRT6, and three mitochondrial sirtuins, SIRT3, SIRT4, and SIRT5, in regulation of diverse metabolic processes.

Show MeSH