Graduate School of Pharmaceutical Sciences, Laboratory of Molecular Metabology, Kyoto University, Kyoto, Japan.
The University of Manchester, Faculty of Biology, Medicine and Health, Oxford Road, Manchester, M13 9PL, UK.
Commun Biol. 2020 May 6;3(1):211. doi: 10.1038/s42003-020-0942-0.
The methyl cycle is a universal metabolic pathway providing methyl groups for the methylation of nuclei acids and proteins, regulating all aspects of cellular physiology. We have previously shown that methyl cycle inhibition in mammals strongly affects circadian rhythms. Since the methyl cycle and circadian clocks have evolved early during evolution and operate in organisms across the tree of life, we sought to determine whether the link between the two is also conserved. Here, we show that methyl cycle inhibition affects biological rhythms in species ranging from unicellular algae to humans, separated by more than 1 billion years of evolution. In contrast, the cyanobacterial clock is resistant to methyl cycle inhibition, although we demonstrate that methylations themselves regulate circadian rhythms in this organism. Mammalian cells with a rewired bacteria-like methyl cycle are protected, like cyanobacteria, from methyl cycle inhibition, providing interesting new possibilities for the treatment of methylation deficiencies.
甲基循环是一种普遍的代谢途径，为核酸和蛋白质的甲基化提供甲基，调节细胞生理的各个方面。我们之前已经表明，哺乳动物的甲基循环抑制强烈影响昼夜节律。由于甲基循环和生物钟在进化早期就已经进化，并在生命之树上的各种生物中发挥作用，我们试图确定两者之间的联系是否也被保守。在这里，我们表明，甲基循环抑制会影响从单细胞藻类到人类等物种的生物节律，这些物种之间的进化时间跨度超过 10 亿年。相比之下，蓝藻生物钟对甲基循环抑制具有抗性，尽管我们证明甲基本身调节该生物的昼夜节律。具有重布线细菌样甲基循环的哺乳动物细胞受到保护，就像蓝藻一样，免受甲基循环抑制的影响，为甲基化缺陷的治疗提供了有趣的新可能性。
