How Clocks See the Light

Abstract

The circadian clocks that regulate daily rhythms in various processes in living organisms are entrained to a 24-hour cycle by mechanisms that detect daily changes in the amount of light in the environment. Hirayama et al . show that hydrogen peroxide (H 2 O 2 ) can function as a required signaling molecule to transmit the sensation of light to changes in timing of the biochemical clock. In zebrafish, oscillators are present in peripheral tissues and organs and are sensitive to exposure to light. Hirayama et al . used Z3 cells (a cell line from zebrafish embryos) to show that exposure of the cells to light caused increased production of H 2 O 2 (which was detected in cells transfected with a fluorescent probe molecule sensitive to oxidation by reactive oxygen species). Exposure of the cells to H 2 O 2 increased expression of zebrafish Cryptochrome and Period genes (which encode components of the core clock machinery) and did so with a time course similar to that observed when cells were exposed to light. Catalase is an antioxidant enzyme that can degrade H 2 O 2 , and the authors confirmed that light stimulated expression of the zCat gene, but it did so with a delayed time course consistent with its possible function in a negative feedback loop to cyclically suppress expression of the clock genes that initially resulted from light-induced generation of H 2 O 2 . In mammalian cells, H 2 O 2 did not influence expression of the clock genes, but then, mammalian peripheral tissues are not responsive to light. What remains unknown is the identity of the actual phototransducer in the zebrafish system. J. Hirayama, S. Cho, P. Sassone-Corsi, Circadian control by the reduction/oxidation pathway: Catalase represses light-dependent clock gene expression in the zebrafish. Proc. Natl. Acad. Sci. U.S.A. 104 , 15747-15752 (2007). [Abstract] [Full Text]