Journal
PHYSIOLOGICAL REVIEWS
Volume 92, Issue 3, Pages 1479-1514Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/physrev.00022.2011
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- NIA NIH HHS [R37 AG028730, R01 AG019719, R01 AG028730] Funding Source: Medline
- NIDDK NIH HHS [DP1 DK098058] Funding Source: Medline
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Nogueiras R, Habegger KM, Chaudhary N, Finan B, Banks AS, Dietrich MO, Horvath TL, Sinclair DA, Pfluger PT, Tschop MH. Sirtuin 1 and Sirtuin 3: Physiological Modulators of Metabolism. Physiol Rev 92: 1479-1514, 2012; doi:10.1152/physrev.00022.2011.-The sirtuins are a family of highly conserved NAD(+)-dependent deacetylases that act as cellular sensors to detect energy availability and modulate metabolic processes. Two sirtuins that are central to the control of metabolic processes are mammalian sirtuin 1 (SIRT1) and sirtuin 3 (SIRT3), which are localized to the nucleus and mitochondria, respectively. Both are activated by high NAD(+) levels, a condition caused by low cellular energy status. By deacetylating a variety of proteins that induce catabolic processes while inhibiting anabolic processes, SIRT1 and SIRT3 coordinately increase cellular energy stores and ultimately maintain cellular energy homeostasis. Defects in the pathways controlled by SIRT1 and SIRT3 are known to result in various metabolic disorders. Consequently, activation of sirtuins by genetic or pharmacological means can elicit multiple metabolic benefits that protect mice from diet-induced obesity, type 2 diabetes, and nonalcoholic fatty liver disease.
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