Liquid–liquid phase separation (LLPS) of biomolecules drives the formation of cellular compartments, which determines cell plasticity and fate decision. Emerging evidence indicates that a large number of membraneless organelles (MLOs), including nucleoli, Cajal bodies, P-bodies, and stress granules, exist as liquid droplets within the cell and orchestrate the cell plasticity control in response to the dynamics of extracellular cues. The MLOs provide not only organizers for signaling cascade but also nano-reactors for signaling catalysis (Liu et al., 2020). However, the molecular mechanisms underlying MLO dynamics and its relation to the cell plasticity control have remained elusive (Alberti and Hyman, 2021). MLO assembly is tightly regulated in the intracellular environment, and failure to control its dynamic properties often leads to protein misfolding and aggregation, which perturbs cell plasticity and elicits pathogenic reaction. In this special issue, we describe the mechanisms and regulation of condensate assembly and dissolution, highlight recent advances in understanding the role of biomolecular condensates in aging and disease, and discuss how cellular stress, aging-related loss of homeostasis, and a decline in protein quality control may contribute to the formation of aberrant, disease-causing condensates.

中文翻译：

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通过相分离协调细胞可塑性


生物分子的液-液相分离（LLPS）驱动细胞区室的形成，这决定了细胞的可塑性和命运决定。新出现的证据表明，大量无膜细胞器（MLO），包括核仁、卡哈尔小体、P-小体和应激颗粒，以液滴形式存在于细胞内，并根据细胞外信号的动态协调细胞可塑性控制。 MLO不仅提供信号级联的组织者，还提供信号催化的纳米反应器（Liu et al., 2020）。然而，MLO 动力学背后的分子机制及其与细胞可塑性控制的关系仍然难以捉摸（Alberti 和 Hyman，2021）。 MLO 组装在细胞内环境中受到严格调控，无法控制其动态特性通常会导致蛋白质错误折叠和聚集，从而扰乱细胞可塑性并引发致病反应。在本期特刊中，我们描述了凝聚体组装和溶解的机制和调节，重点介绍了理解生物分子凝聚体在衰老和疾病中的作用的最新进展，并讨论了细胞应激、衰老相关的稳态丧失和蛋白质下降如何影响质量控制可能会导致异常、致病的冷凝物的形成。