昼夜节律与自噬相互调控的机制

Mechanism underlying the mutual regulation between circadian rhythm and autophagy

背景:目前,昼夜节律性自噬已逐渐成为生命科学和人类健康的研究热点,其在维持人类健康方面起着重要的作用,且诸多研究已证实昼夜节律紊乱导致的异常自噬会诱发各种疾病,如神经退行性变、癌症、衰老过程、自身免疫等。随着研究的深入,自噬与昼夜节律调节之间相关联的证据越来越多,但其相互调控机制尚未阐明。目的:探讨昼夜节律与自噬的关系,综述分子生物钟、自噬的昼夜节律、及昼夜节律与自噬相互调控机制的最新研究进展,并对其具体分子机制进行详细的概述。方法:以“circadian rhythm,autophagy,molecular circadian clock,regulation,gene”为英文主题词,以“昼夜节律,自噬,分子生物钟,调控机制,基因”为中文主题词,分别在PubMed数据库、Web of Science、中国知网以及万方数据库检索最新的相关中英文文献,根据纳入及排除标准最终纳入107篇文献进行归纳总结。结果与结论:①昼夜节律是由分子生物钟产生的24 h生理和行为节律,分子生物钟与其产生密切相关,主要是通过BMAL1:CLOCK异源二聚体与靶分子启动子中的E-box结合,进一步激活Cry、Per、Rev-erb和Ror基因的转录,从而介导昼夜节律的产生;②一些参与自噬的基因、转录因子和通路在昼夜变化中具有节律性,其受多个昼夜节律生物钟核心成分(如Per2、BMAL1和REV-ERB)的调控,是功能上连接昼夜节律和自噬的桥梁;③此外,一些分子与药物也能影响自噬和昼夜节律,在节律性自噬的调控中起着至关重要的作用。

BACKGROUND:At present,circadian rhythm of autophagy has gradually become a research hotspot in life sciences and human health.It plays an important role in maintaining human health,and many studies have confirmed that abnormal autophagy caused by circadian rhythm disorders can induce various diseases,such as neurodegeneration,cancer,aging,and autoimmunity.With the in-depth research,there is increasing evidence for the regulatory association between autophagy and circadian rhythm.However,their mutual regulation mechanism has not yet been elucidated.OBJECTIVE:To explore the relationship between circadian rhythm and autophagy,review the latest research progress in molecular circadian clock,circadian rhythm of autophagy,and the mutual regulation mechanism of circadian rhythm and autophagy,thereby giving a detailed overview of the specific molecular mechanism.METHODS:“Circadian rhythm,autophagy,molecular circadian clock,regulation,gene”were used as English and Chinese search terms.Relevant literature was searched in the PubMed,Web of Science,CNKI,and WanFang Databases.Finally,107 articles were included for review according to the inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Circadian rhythm is a 24-hour physiological and behavioral rhythm generated by the molecular circadian clock.The molecular circadian clock is closely related to its production,mainly through the binding of BMAL1:CLOCK heterodimer to the E-box in the target molecule promoter to further activate the transcription of Cry,Per,Rev-erb,and Ror genes,thereby modulating the production of circadian rhythms.(2)Some genes,transcription factors,and pathways involved in autophagy are rhythmic in circadian changes,regulated by multiple circadian clock core components(such as Per2,BMAL1,and REV-ERB),which are a bridge functionally linking circadian rhythms and autophagy.(3)In addition,some molecules and drugs can also affect autophagy and circadian rhythm and play a crucial role in the regulation of rhythmic autophagy.