AMPK Regulates the Circadian Clock by Cryptochrome Phosphorylation and Degradation

Abstract

Coupling Clocks and Metabolism Circadian clocks in mammals coordinate behavior and physiology with daily light-dark cycles by driving rhythmic transcription of thousands of genes. The master clock in the brain is set by light, but clocks in peripheral tissues, such as the liver, are set by daily feeding. Such coupling should allow tissues to “anticipate” food consumption and optimize the timing of metabolic processes, but how nutritional status is communicated to peripheral clocks is unclear. Studying cell culture models and mice, Lamia et al. (p. 437 ; see the Perspective by Suter and Schibler ) show that the nutrient-responsive signaling molecule AMPK (AMP-activated protein kinase) provides metabolic information to circadian clocks by triggering phosphorylation and subsequent degradation of the clock component cryptochrome-1. Thus—cryptochromes, which originally evolved as blue-light photoreceptors in plants, act as chemical energy sensors in mammals.