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Daily magnesium fluxes regulate cellular timekeeping and energy balance

机译：每日的镁通量调节细胞的计时和能量平衡

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摘要

Circadian clocks are fundamental to the biology of most eukaryotes, coordinating behaviour and physiology to resonate with the environmental cycle of day and night through complex networks of clock-controlled genes(1-3). A fundamental knowledge gap exists, however, between circadian gene expression cycles and the biochemical mechanisms that ultimately facilitate circadian regulation of cell biology(4,5). Here we report circadian rhythms in the intracellular concentration of magnesium ions, [Mg2+]i, which act as a cell-autonomous timekeeping component to determine key clock properties both in a human cell line and in a unicellular alga that diverged from each other more than 1 billion years ago(6). Given the essential role of Mg2+ as a cofactor for ATP, a functional consequence of [Mg2+] i oscillations is dynamic regulation of cellular energy expenditure over the daily cycle. Mechanistically, we find that these rhythms provide bilateral feedback linking rhythmic metabolism to clock-controlled gene expression. The global regulation of nucleotide triphosphate turnover by intracellular Mg2+ availability has potential to impact upon many of the cell's more than 600 MgATP-dependent enzymes(7) and every cellular system where MgNTP hydrolysis becomes rate limiting. Indeed, we find that circadian control of translation by mTOR(8) is regulated through [Mg2+] i oscillations. It will now be important to identify which additional biological processes are subject to this form of regulation in tissues of multicellular organisms such as plants and humans, in the context of health and disease.
机译：昼夜节律是大多数真核生物生物学的基础，它通过复杂的时钟控制基因网络协调行为和生理，以与昼夜环境周期产生共鸣（1-3）。然而，在昼夜节律基因表达周期与最终促进昼夜节律对细胞生物学调控的生化机制之间存在基本的知识鸿沟（4,5）。在这里，我们报告了镁离子[Mg2 +] i在细胞内浓度的昼夜节律，镁离子作为细胞自主的计时组件，可确定人细胞系和单细胞藻类中彼此之间的差异更大的关键时钟特性。 10亿年前（6）。考虑到Mg2 +作为ATP的辅助因子所起的重要作用，[Mg2 +] i振荡的功能结果是动态调节细胞在整个周期内的能量消耗。从机理上讲，我们发现这些节律提供了将节律代谢与时钟控制的基因表达联系起来的双边反馈。细胞内Mg2 +的可用性对三磷酸核苷酸代谢的全球调控可能会影响细胞中600多种MgATP依赖性酶[7]和MgNTP水解成为速率限制的每个细胞系统。实际上，我们发现mTOR（8）的昼夜节律控制是通过[Mg2 +] i振荡来调节的。现在，重要的是要在健康和疾病的背景下，确定多细胞生物（例如植物和人）的组织中哪些额外的生物过程受到这种形式的调节。

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  • 来源
    《Nature》 |2016年第7599期|375-379|共5页
  • 作者

    Feeney Kevin A.; Hansen Louise L.; Putker Marrit; Olivares-Yanez Consuelo; Day Jason; Eades Lorna J.; Larrondo Luis F.; Hoyle Nathaniel P.; ONeill John S.; van Ooijen Gerben;

  • 作者单位

    MRC Lab Mol Biol, Francis Crick Ave,Biomed Campus, Cambridge CB2 0QH, England;

    Univ Edinburgh, Sch Biol Sci, Max Born Crescent, Edinburgh EH9 3BF, Midlothian, Scotland;

    MRC Lab Mol Biol, Francis Crick Ave,Biomed Campus, Cambridge CB2 0QH, England;

    Pontificia Univ Catolica Chile, Fac Ciencias Biol, Dept Genet Mol & Microbiol, Millennium Nucleus Fungal Integrat & Synthet Biol, Casilla 114-D, Santiago, Chile;

    Univ Cambridge, Dept Earth Sci, Downing St, Cambridge CB2 3EQ, England;

    Univ Edinburgh, Sch Chem, David Brewster Rd, Edinburgh EH9 3FJ, Midlothian, Scotland;

    Pontificia Univ Catolica Chile, Fac Ciencias Biol, Dept Genet Mol & Microbiol, Millennium Nucleus Fungal Integrat & Synthet Biol, Casilla 114-D, Santiago, Chile;

    MRC Lab Mol Biol, Francis Crick Ave,Biomed Campus, Cambridge CB2 0QH, England;

    MRC Lab Mol Biol, Francis Crick Ave,Biomed Campus, Cambridge CB2 0QH, England;

    Univ Edinburgh, Sch Biol Sci, Max Born Crescent, Edinburgh EH9 3BF, Midlothian, Scotland;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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