title: Comparing and contrasting the roles of AMPK and SIRT1 in metabolic tissues.
abstract: The ability to adapt and respond to nutrients is an ancient cellular function, conserved from unicellular to the most complex multicellular organisms, including mammals. Mammals adapt to changes in nutritional status through the modulation of tissue-specific metabolic pathways so as to maintain energy homeostasis. At least two proteins are activated in response to reduced nutrient availability: AMP-activated protein kinase (AMPK) and NAD(+)-dependent deacetylase SIRT1. AMPK functions as a sensor of cellular energy status and as a master regulator of metabolism. When ATP levels decrease, AMPK is activated to boost ATP production and to inhibit ATP usage, thus restoring energy balance. Similarly, SIRT1 is activated in response to changes in the energy status to promote transcription of genes that mediate the metabolic response to stress, starvation or calorie restriction. Several observations support a model where, in response to stress and reduced nutrients, a metabolic pathway is activated within which AMPK and SIRT1 concordantly function to ensure an appropriate cellular response and adaptation to environmental modifications. In this perspective, we compare and contrast the roles of SIRT1 and AMPK in several metabolic tissues and propose a working model of how the AMPK-SIRT1 axis may be regulated to control functions relevant to organismal physiology and pathophysiology.
authors.affiliation: Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Marcella
authors.initials: M
authors.lastname: Fulco
authors.forename: Vittorio
authors.initials: V
authors.lastname: Sartorelli
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000375:Aging / Q000473:pathology; D000818:Animals; D006801:Humans; D008954:Models, Biological; D009928:Organ Specificity; D037761:Sirtuins / Q000378:metabolism*
chemical_list: D055372:AMP-Activated Protein Kinases; D037761:Sirtuins