Rhythms in energy storage control the ability of the cyanobacterial circadian clock to reset.
Rhythms in energy storage control the ability of the cyanobacterial circadian clock to reset.
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DOI：
10.1016/j.cub.2014.07.022
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发表时间：
2014-08-18
期刊：
影响因子：
9.2
通讯作者：
Rust, Michael J.
中科院分区：
文献类型：
--
作者：
Pattanayak, Gopal K.;Phong, Connie;Rust, Michael J.
生物钟是一种振荡系统，它安排生物体行为的日常节奏。时钟响应外部信号重置其相位的能力对于与环境适当同步至关重要。在蓝藻模型时钟中，构成核心振荡器的KaiABC蛋白对代谢物直接敏感。ATP/ADP比值降低和氧化醌在体外引起时钟相移。但目前尚不清楚是什么决定了细胞对黑暗的代谢反应，从而决定了生物钟重置的幅度。我们表明，蓝藻生物钟在新陈代谢中产生一种节奏，导致细胞在夜幕降临前积累糖原。组氨酸激酶CikA的突变通过错误调节全基因组的时钟输出产生不敏感的时钟输入表型，导致糖原过度积累，随后在黑暗中产生高ATP。相反，我们发现破坏糖原代谢导致黑暗中ATP降低，使生物钟对黑暗脉冲敏感。观察到的细胞能量变化足以在体外时钟模型中概括相移表型。我们的研究结果表明，时钟输入表型可以由代谢失调引起，并说明了昼夜节律生物学的框架，其中时钟输出通过代谢反馈以控制输入机制。
Circadian clocks are oscillatory systems that schedule daily rhythms of organismal behavior. The ability of the clock to reset its phase in response to external signals is critical for proper synchronization with the environment. In the model clock from cyanobacteria, the KaiABC proteins that comprise the core oscillator are directly sensitive to metabolites. Reduced ATP/ADP ratio and the oxidized quinones cause clock phase shifts in vitro. But it is unclear what determine the metabolic response of the cell to darkness and thus the magnitude of clock resetting. We show that the cyanobacterial circadian clock generates a rhythm in metabolism that causes cells to accumulate glycogen in anticipation of nightfall. Mutation of the histidine kinase CikA creates an insensitive clock input phenotype by misregulating clock output genome-wide, leading to over-accumulation of glycogen and subsequently high ATP in the dark. Conversely, we show that disrupting glycogen metabolism results in low ATP in the dark and makes the clock hypersensitive to dark pulses. The observed changes in cellular energy are sufficient to recapitulate phase shifting phenotypes in an in vitro model of the clock. Our results show that clock input phenotypes can arise from metabolic dysregulation and illustrate a framework for circadian biology where clock outputs feed back through metabolism to control input mechanisms.
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影响因子：
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作者：
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发表时间：
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影响因子：
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