Circadian rhythms in plants and animals appear to be coupled to periodic changes in activity of metabolic pathways (see the Perspective by Imaizumi et al.). Yin et al. describe a molecular mechanism that may contribute to the coordination of these biochemical processes. Rev-erbα controls transcription of the gene encoding the circadian clock component Bmal1. Rev-erbα binds to and is regulated by heme, which stabilizes Rev-erbα in a repressor complex, which in turn can block production of gluconeogenic enzymes. Thus, Rev-erbα acts as a heme sensor to coordinate the cellular clock, glucose homeostasis, and energy metabolism in human liver cells. Studying Arabidopsis, Dodd et al. now show that a cytoplasmic signaling molecule, cyclic adenosine diphosphate ribose (cADPR), is also a component of the clock mechanism. Perturbations to the feedback loop including cADPR result in instabilities in the clock and disruptions in the daily oscillations of cytoplasmic Ca2+ release.
L. Yin, N. Wu, J. C. Curtin, M. Qatanani, N. R. Szwergold, R. A. Reid, G. M. Waitt, D. J. Parks, K. H. Pearce, G. B. Wisely, M. A. Lazar, Rev-erbα, a heme sensor that coordinates metabolic and circadian pathways. Science 318, 1786-1789 (2007). [Abstract] [Full Text]
A. N. Dodd, M. J. Gardner, C. T. Hotta, K. E. Hubbard, N. Dalchau, J. Love, J.-M. Assie, F. C. Robertson, M. K. Jakobsen, J. Gonçalves, D. Sanders, A. A. R. Webb, The Arabidopsis circadian clock incorporates a cADPR-based feedback loop. Science 318, 1789-1792 (2007). [Abstract] [Full Text]