DRP1活性的昼夜节律调控线粒体动力学和生物能量学

Circadian Control of DRP1 Activity Regulates Mitochondrial Dynamics and Bioenergetics.

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|核心内容：

线粒体裂变-融合动力学和线粒体生物能量学，包括氧化磷酸化和ATP的产生，都受到强烈的时钟控制。

在这里，我们表明，这些昼夜振荡依赖于动力蛋白相关蛋白1(DRP1)的昼夜节律调节，动力相关蛋白1是线粒体分裂的关键介质。

我们结合使用了体外和体内模型，包括人皮肤成纤维细胞和Drp1缺陷或时钟缺陷小鼠，以表明这些动力学是通过Drp1的昼夜节律控制的。

基因或药物上取消了DRP1活性，取消了昼夜节律网络动力学和线粒体呼吸活性，并消除了昼夜ATP的产生。

药物沉默调节昼夜新陈代谢和线粒体功能的通路(如sirtuins，AMPK)也改变了DRp1的磷酸化，并且DRp1活性的丧失损害了昼夜节律功能。

我们的发现为线粒体网络和生理周期之间的串扰提供了新的见解。

原文摘要：

Mitochondrial fission-fusion dynamics and mitochondrial bioenergetics, including oxidative phosphorylation and generation of ATP, are strongly clock controlled. Here we show that these circadian oscillations depend on circadian modification of dynamin-related protein 1 (DRP1), a key mediator of mitochondrial fission. We used a combination of in vitro and in vivo models, including human skin fibroblasts and DRP1-deficient or clock-deficient mice, to show that these dynamics are clock controlled via circadian regulation of DRP1. Genetic or pharmacological abrogation of DRP1 activity abolished circadian network dynamics and mitochondrial respiratory activity and eliminated circadian ATP production. Pharmacological silencing of pathways regulating circadian metabolism and mitochondrial function (e.g., sirtuins, AMPK) also altered DRP1 phosphorylation, and abrogation of DRP1 activity impaired circadian function. Our findings provide new insight into the crosstalk between the mitochondrial network and circadian cycles.

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参考文献：https://www.cell.com/cell-metabolism/pdf/S1550-4131(18)30063-9.pdf

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