title: AMPK at the crossroads of circadian clocks and metabolism.
abstract: Circadian clocks coordinate behavior and physiology with daily environmental cycles and thereby optimize the timing of metabolic processes such as glucose production and insulin secretion. Such circadian regulation of metabolism provides an adaptive advantage in diverse organisms. Mammalian clocks are primarily based on a transcription and translation feedback loop in which a heterodimeric complex of the transcription factors CLOCK (circadian locomotor output cycles kaput) and BMAL1 (brain and muscle Arnt-like protein 1) activates the expression of its own repressors, the period (PER1-3) and cryptochrome (CRY1 and CRY2) proteins. Posttranslational modification of these core clock components is critical for setting clock time or adjusting the speed of the clock. AMP-activated protein kinase (AMPK) is one of several metabolic sensors that have been reported to transmit energy-dependent signals to the mammalian clock. AMPK does so by driving the phosphorylation and destabilization of CRY and PER proteins. In addition, AMPK subunit composition, sub-cellular localization, and substrate phosphorylation are dependent on clock time. Given the well-established role of AMPK in diverse aspects of metabolic physiology, the reciprocal regulation of AMPK and circadian clocks likely plays an important role in circadian metabolic regulation.
authors: The Scripps Research Institute, Department of Chemical Physiology, La Jolla, CA 92037, USA.
authors: Sabine D
authors: SD
authors: Jordan
authors: Katja A
authors: KA
authors: Lamia
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism; D057906:Circadian Clocks / Q000502:physiology*; D056931:Cryptochromes / Q000235:genetics / Q000378:metabolism; D025461:Feedback, Physiological / Q000502:physiology*; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction / Q000502:physiology
chemical_list: D056930:ARNTL Transcription Factors; D056931:Cryptochromes; D007328:Insulin; D056950:Period Circadian Proteins; D056926:CLOCK Proteins; D055372:AMP-Activated Protein Kinases; D005947:Glucose