昼夜节律
生物
生物钟
蛋白质组
细胞生物学
蛋白质周转
平衡
功能(生物学)
蛋白质生物合成
神经科学
生物信息学
生物化学
作者
Alessandra Stangherlin,Estere Seinkmane,John S. O’Neill
标识
DOI:10.1016/j.coisb.2021.100391
摘要
Circadian rhythms are ∼24 h cycles of organismal and cellular activity ubiquitous to mammalian physiology. A prevailing paradigm suggests that timing information flows linearly from rhythmic transcription via protein abundance changes to drive circadian regulation of cellular function. Challenging this view, recent evidence indicates daily variation in many cellular functions arises through rhythmic post-translational regulation of protein activity. We suggest cellular circadian timing primarily functions to maintain proteome homeostasis rather than perturb it. Indeed, although relevant to timekeeping mechanism, daily rhythms of clock protein abundance may be the exception, not the rule. Informed by insights from yeast and mammalian models, we propose that optimal bioenergetic efficiency results from coupled rhythms in mammalian target of rapamycin complex activity, protein synthesis/turnover, ion transport and protein sequestration, which drive facilitatory rhythms in metabolic flux and substrate utilisation. Such daily consolidation of proteome renewal would account for many aspects of circadian cell biology whilst maintaining osmotic homeostasis.
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