Temporal orchestration of circadian autophagy rhythm by C/EBPβ
Temporal orchestration of circadian autophagy rhythm by C/EBPβ
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DOI：
10.1038/emboj.2011.322
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发表时间：
2011-11-16
期刊：
影响因子：
11.4
通讯作者：
Lin, Jiandie D.
中科院分区：
文献类型：
--
作者：
Ma, Di;Panda, Satchidananda;Lin, Jiandie D.
组织代谢的时间组织对于维持哺乳动物体内营养和能量的稳态是重要的。自噬是一种保守的细胞途径，其响应于营养限制而被激活，导致细胞质组分的降解以及氨基酸和其他营养物质的释放。在这里，我们表明，自噬在小鼠肝脏中表现出强大的昼夜节律，这是伴随着参与自噬各个步骤的基因的周期性诱导。转录因子和辅因子的功能分析确定C/EBP β是自噬的有效激活剂。C/EBP β在肝脏中有节奏地表达，并受昼夜节律和营养信号的调节。在培养的原代肝细胞中，C/EBP β刺激自噬基因表达程序，足以激活自噬蛋白降解。腺病毒介导的C/EBP β体内RNAi敲低消除了肝脏中的昼夜自噬节律。此外，C/EBP β和自噬的昼夜调节在缺乏功能性肝脏时钟的小鼠中被破坏。因此，我们已经确定C/EBP β是将自噬与生物钟联系起来并在整个光/暗周期中维持营养稳态的关键因素。The EMBO Journal（2011）30，4642-4651. doi：10.1038/doj.2011.322; 2011年9月6日在线发布
Temporal organization of tissue metabolism is important for maintaining nutrient and energy homeostasis in mammals. Autophagy is a conserved cellular pathway that is activated in response to nutrient limitation, resulting in the degradation of cytoplasmic components and the release of amino acids and other nutrients. Here, we show that autophagy exhibits robust circadian rhythm in mouse liver, which is accompanied by cyclic induction of genes involved in various steps of autophagy. Functional analyses of transcription factors and cofactors identified C/EBP beta as a potent activator of autophagy. C/EBP beta is rhythmically expressed in the liver and is regulated by both circadian and nutritional signals. In cultured primary hepatocytes, C/EBP beta stimulates the program of autophagy gene expression and is sufficient to activate autophagic protein degradation. Adenoviral-mediated RNAi knockdown of C/EBP beta in vivo abolishes diurnal autophagy rhythm in the liver. Further, circadian regulation of C/EBP beta and autophagy is disrupted in mice lacking a functional liver clock. We have thus identified C/EBP beta as a key factor that links autophagy to biological clock and maintains nutrient homeostasis throughout light/dark cycles. The EMBO Journal (2011) 30, 4642-4651. doi: 10.1038/emboj.2011.322; Published online 6 September 2011