Aging Institute, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Aging Institute, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Exp Cell Res. 2021 Mar 1;400(1):112515. doi: 10.1016/j.yexcr.2021.112515. Epub 2021 Feb 11.
Metabolite fluctuations following nutrient metabolism or environmental stresses impact various intracellular signaling networks and stress responses to maintain cellular and organismal homeostasis. It has been shown that subcellular organelles, such as the endoplasmic reticulum, the Golgi apparatus, lysosomes and mitochondria serve as crucial hubs linking alterations in metabolite levels to cellular responses. This role is coordinated by molecular machineries that are associated with the lipid membranes of organelles, which sense the fluctuations in specific metabolites and activate the appropriate signaling and effector molecules. Moreover, recent studies have demonstrated that membraneless organelles, such as the nucleolus and stress granules, are involved in the metabolic stress response. Metabolite-induced post-translational modifications appear to play an important role in this process. Here, we review the molecular mechanisms of metabolite sensing and metabolite-mediated stress responses through membrane-bound and membraneless organelles in mammalian cells.
代谢物波动会影响各种细胞内信号网络和应激反应，以维持细胞和机体的内稳态。有研究表明，细胞内的细胞器，如内质网、高尔基体、溶酶体和线粒体等，作为连接代谢物水平变化与细胞反应的关键枢纽。这种作用是由与细胞器的脂膜相关的分子机制来协调的，这些分子机制可以感知特定代谢物的波动，并激活适当的信号和效应分子。此外，最近的研究表明，无膜细胞器，如核仁、应激颗粒等，也参与了代谢应激反应。代谢物诱导的翻译后修饰似乎在这个过程中起着重要作用。在这里，我们综述了哺乳动物细胞中通过膜结合和无膜细胞器来感知代谢物和代谢物介导的应激反应的分子机制。
