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The ultradian clock: not to be confused with the cell cycle

Nature Reviews Molecular Cell Biology volume 7, page 1 (2006)Cite this article

Biochemical reactions that constitute the metabolic network generally have relaxation times in the range of 0.1 ms to 100 s, and are but one component of the massively interconnected web of the total cellular system1,2. For at least 5 decades, this system has been referred to as a temporal hierarchy, but as pointed out by Yates3, it is really a heterarchy in which the levels of organization are not separately and clearly defined, but interact strongly at every level and even directly between widely separated levels. The time structure of life4 is at least as complex as it its spatial structure — but, whereas the spatial structure is documented precisely to Å resolution for many macromolecules and we have extensive information on subcellular ultrastructure, our appreciation of the temporal organization is less impressive. Details of molecular dynamics and enzyme kinetics have been examined in vitro until recently, but with the development of new non-invasive imaging techniques, they are now increasingly studied in vivo. Rapid progress towards minimizing our ignorance is being made even on a μs time-scale resolution5.

Despite the clarity and astonishing spatial resolution of medical imaging techniques, the direct non-invasive probing of the whole organism is rather less feasible6. The system developed by Kuriyama and his colleagues using a self-synchronized continuous culture of yeast7 provides a unique opportunity to extend our understanding of the minute-to-minute development of the organism through multiple cycles in experiments that might be continued for days, weeks or months. The unperturbed progression of state changes can be monitored, as if in a single organism, although the population density is 109 yeasts cells per ml. So, there is plenty of both cellular and extracellular material for discrete time samples for biochemical analysis. So far, 15 papers have been published, and the essential discoveries recently reviewed8,9. In a nutshell, the picture that emerges is one of an exquisitely and intensively interwoven network of temporal controls that encompass every aspect of cellular function, including electron transport, membrane transport, energy transduction, metabolism, biosynthesis transcription, membrane translation and ribosome assembly, organelle biogenesis, membrane flux and trafficking, and nuclear and cell-division cycle progression10. Most importantly, the entire system is tied to a metronomic time-base (in yeast, a 40-min interval) that provides a simplifying principle, a temporal ordering to the enormous complexity of the living state. Strong evidence for a similar organization of the time structures of other yeasts and protists has been summarized11.

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  1. Microbiology, Main Building, Cardiff School of Biosciences, P.O. Box 915, Cardiff University, Wales, CF10 3TL, UK

    David Lloyd

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Lloyd, D. The ultradian clock: not to be confused with the cell cycle. Nat Rev Mol Cell Biol 7, 1 (2006). https://doi.org/10.1038/nrm1980-c1

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