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冬天即将来临:酶聚合在休眠和疾病中对细胞代谢的调控。

Winter is coming: Regulation of cellular metabolism by enzyme polymerization in dormancy and disease.

机构信息

Helsinki Institute of Life Science, HiLIFE, University of Helsinki, Finland; Research Programme in Molecular and Integrative Biosciences, Faculty of Biological and Environmental Sciences, University of Helsinki, Finland.

Helsinki Institute of Life Science, HiLIFE, University of Helsinki, Finland; Research Programme in Molecular and Integrative Biosciences, Faculty of Biological and Environmental Sciences, University of Helsinki, Finland; Neuroscience Center, University of Helsinki, Finland.

出版信息

Exp Cell Res. 2020 Dec 15;397(2):112383. doi: 10.1016/j.yexcr.2020.112383. Epub 2020 Nov 17.

DOI:10.1016/j.yexcr.2020.112383
PMID:33212148
Abstract

Metabolism feeds growth. Accordingly, metabolism is regulated by nutrient-sensing pathways that converge growth promoting signals into biosynthesis by regulating the activity of metabolic enzymes. When the environment does not support growth, organisms invest in survival. For cells, this entails transitioning into a dormant, quiescent state (G0). In dormancy, the activity of biosynthetic pathways is dampened, and catabolic metabolism and stress tolerance pathways are activated. Recent work in yeast has demonstrated that dormancy is associated with alterations in the physicochemical properties of the cytoplasm, including changes in pH, viscosity and macromolecular crowding. Accompanying these changes, numerous metabolic enzymes transition from soluble to polymerized assemblies. These large-scale self-assemblies are dynamic and depolymerize when cells resume growth. Here we review how enzyme polymerization enables metabolic plasticity by tuning carbohydrate, nucleic acid, amino acid and lipid metabolic pathways, with particular focus on its potential adaptive value in cellular dormancy.

摘要

新陈代谢为生长提供养分。因此,新陈代谢受到营养感应途径的调节,这些途径通过调节代谢酶的活性将促进生长的信号集中到生物合成中。当环境不支持生长时,生物体就会投入到生存中。对于细胞来说,这需要进入休眠、静止状态(G0)。在休眠状态下,生物合成途径的活性受到抑制,而分解代谢和应激耐受途径被激活。最近在酵母中的研究表明,休眠与细胞质的物理化学性质的改变有关,包括 pH 值、粘度和大分子拥挤度的变化。伴随着这些变化,许多代谢酶从可溶性状态转变为聚合状态。这些大规模的自组装是动态的,当细胞恢复生长时会解聚。在这里,我们回顾了酶聚合如何通过调节碳水化合物、核酸、氨基酸和脂质代谢途径来实现代谢可塑性,特别关注其在细胞休眠中的潜在适应性价值。

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