Sirtuin 1 and sirtuin 3: physiological modulators of metabolism.
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.
Department of Physiology, School of Medicine-Instituto de Investigaciones Sanitarias, University of Santiago de Compostela, Santiago de Compostela, Spain.
Ruben
R
Nogueiras
Kirk M
KM
Habegger
Nilika
N
Chaudhary
Brian
B
Finan
Alexander S
AS
Banks
Marcelo O
MO
Dietrich
Tamas L
TL
Horvath
David A
DA
Sinclair
Paul T
PT
Pfluger
Matthias H
MH
Tschöp
D000818:Animals; D002940:Circadian Rhythm; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology; D020022:Genetic Predisposition to Disease; D006706:Homeostasis; D006801:Humans; D008659:Metabolic Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D010641:Phenotype; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D056566:Sirtuin 3 / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
D020536:Enzyme Activators; D056564:Sirtuin 1; D056566:Sirtuin 3