The study by Lamia et al. investigates the role of adenosine monophosphate-activated protein kinase (AMPK) in regulating circadian clocks, particularly focusing on the phosphorylation and degradation of cryptochrome 1 (CRY1). AMPK, a nutrient-responsive kinase, was found to phosphorylate CRY1 at serine 71 (S71) and serine 280 (S280), which alters the stability of CRY1. In mouse fibroblasts, AMPK activity and nuclear localization were rhythmic and inversely correlated with CRY1 nuclear protein abundance. Stimulation of AMPK led to the destabilization of cryptochromes and altered circadian rhythms. Genetic disruption of the AMPK pathway in mice resulted in alterations in peripheral clocks. The study also found that AMPK activation shifts the phase of entrainment in mouse fibroblasts and livers, and that AMPK is rhythmic in mouse livers, with its nuclear import regulated by the diurnal expression of the regulatory subunit AMPKβ2. In vivo experiments showed that AMPK activation reduced endogenous CRY1 levels, and loss of AMPK signaling in hepatocytes disrupted circadian rhythms. These findings suggest that AMPK-mediated phosphorylation of CRY1 contributes to the metabolic control of light-independent peripheral circadian clocks.The study by Lamia et al. investigates the role of adenosine monophosphate-activated protein kinase (AMPK) in regulating circadian clocks, particularly focusing on the phosphorylation and degradation of cryptochrome 1 (CRY1). AMPK, a nutrient-responsive kinase, was found to phosphorylate CRY1 at serine 71 (S71) and serine 280 (S280), which alters the stability of CRY1. In mouse fibroblasts, AMPK activity and nuclear localization were rhythmic and inversely correlated with CRY1 nuclear protein abundance. Stimulation of AMPK led to the destabilization of cryptochromes and altered circadian rhythms. Genetic disruption of the AMPK pathway in mice resulted in alterations in peripheral clocks. The study also found that AMPK activation shifts the phase of entrainment in mouse fibroblasts and livers, and that AMPK is rhythmic in mouse livers, with its nuclear import regulated by the diurnal expression of the regulatory subunit AMPKβ2. In vivo experiments showed that AMPK activation reduced endogenous CRY1 levels, and loss of AMPK signaling in hepatocytes disrupted circadian rhythms. These findings suggest that AMPK-mediated phosphorylation of CRY1 contributes to the metabolic control of light-independent peripheral circadian clocks.