The phosphorylation site is specific for AMPK, which acts like a gas gauge by sensing how much energy a cell has. When a cell has plenty of energy, AMPK remains inactive and the cell carries out its normal processes. Her experiments revealed that if a cell runs on empty, AMPK is turned on and attaches a phosphate molecule to CRY1, which initiates the destruction of CRY1. As a result the circadian rhythm speeds up and the clock is reset.

"The insertion of an AMPK phosphorylation site transformed a light sensor into an energy sensor, which now allows nutrients to provide metabolic input to circadian clocks," explain Lamia. "Insertion of a novel sensor into an existing signaling pathway is a very elegant solution to a rather complicated problem."

Genetic inactivation of AMPK in mice blocks these effects, stabilizing CRY1 and severely disrupting peripheral clocks. In contrast, treating mice with AICAR, a synthetic drug that directly activates AMPK, reset the clock in cultured cells as well as in animals, confirming that cryptochromes act as energy sensors that allow to circadian clocks.

Researchers who also contributed to the study include Uma M. Sachdeva and Craig B. Thompson at the Abramson Family Cancer Research Institute at the University of Pennsylvania School of Medicine in Philadelphia, Daniel F. Egan, Debbie S. Vasquez and Reuben Shaw in the Molecular and Cell Biology Laboratory, Elliot C. Williams and Henry Juguilon in the Gene Expression Laboratory as well as Luciano DiTacchio and Satchidananda Panda in the Regulatory Biology Laboratory, all at the Salk Institute for Biological Studies in La Jolla.

Source: Salk Institute