生物钟
线粒体
细胞生物学
线粒体分裂
昼夜节律
生物
时钟
线粒体融合
线粒体DNA
生物化学
基因
内分泌学
作者
Lirong Xu,Qianyun Cheng,Bingxuan Hua,Tingting Cai,Jiaxin Lin,Gongsheng Yuan,Zuoqin Yan,Xiaobo Li,Ning Sun,Chao Lü,Qian Ran
摘要
Abstract Many daily activities are under the control of circadian clock, including nutrition metabolism and energy generation. Mitochondria, as the core factories of oxidizing substrates and producing ATP, undergo changes in quantity and morphology to adapt to the demand for energy. It has been demonstrated that mitochondrial gene expression, dynamics and functions are all affected by circadian clock. Here, we demonstrated that circadian gene Clock affects the number, architecture and function of mitochondria via posttranscriptional regulation of Drp1. Clock Δ19 leads to fragmented mitochondria accompanied with the loss of membrane potential, excessive ROS accumulation and decreased mitochondrial respiration and ATP generation. Clock Δ19 mice exhibit disordered lipid metabolism and evident nonalcoholic fatty liver disease (NAFLD), which are rescued by treatment with the mitochondrial fission inhibitor Mdivi-1. These results suggest a strong relationship between Clock, mitochondrial dynamics and metabolic diseases and provide a new perspective on disordered circadian clock and related diseases.
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