Membraneless organelles in health and disease:exploring the molecular basis,physiological roles and pathological implications

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外文摘要：Once considered unconventional cellular structures,membraneless organelles(MLOs),cellular substructures involved in biological processes or pathways under physiological conditions,have emerged as central players in cellular dynamics and function.MLOs can be formed through liquid-liquid phase separation(LLPS),resulting in the creation of condensates.From neurodegenerative disorders,cardiovascular diseases,aging,and metabolism to cancer,the influence of MLOs on human health and disease extends widely.This review discusses the underlying mechanisms of LLPS,the biophysical properties that drive MLO formation,and their implications for cellular function.We highlight recent advances in understanding how the physicochemical environment,molecular interactions,and post-translational modifications regulate LLPS and MLO dynamics.This review offers an overview of the discovery and current understanding of MLOs and biomolecular condensate in physiological conditions and diseases.This article aims to deliver the latest insights on MLOs and LLPS by analyzing current research,highlighting their critical role in cellular organization.The discussion also covers the role of membrane-associated condensates in cell signaling,including those involving T-cell receptors,stress granules linked to lysosomes,and biomolecular condensates within the Golgi apparatus.Additionally,the potential of targeting LLPS in clinical settings is explored,highlighting promising avenues for future research and therapeutic interventions.

作者：

Yangxin Li、Yuzhe Liu、Xi-Yong Yu、Yan Xu、Xiangbin Pan、Yi Sun、Yanli Wang、Yao-Hua Song、Zhenya Shen

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作者单位：

Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science,State Key Laboratory of Radiation Medicine and Protection,Suzhou Medical College,Collaborative Innovation Center of Hematology,Soochow University,Suzhou,Jiangsu 215123,P.R.China

Department of Orthopedics,The Second Hospital of Jilin University,Changchun,Jilin 130041,P.R.China

NMPA Key Laboratory for Clinical Research and Evaluation of Drug for Thoracic Diseases,Key Laboratory of Molecular Target& Clinical Pharmacology and the State Key Laboratory of Respiratory Disease,School of Pharmaceutical Sciences,Guangzhou Medical University,Guangzhou 511436,P.R.China

Department of General Medicine,The Second Xiangya Hospital,Central South University,Changsha,Hunan 410011,P.R.China

Department of Structural Heart Disease,National Center for Cardiovascular Disease,China & Fuwai Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College,State key laboratory of cardiovascular disease,Beijing 100037,P.R.China

Department of Cardiovascular Surgery,Fuwai Yunnan Cardiovascular Hospital,Kunming 650102,P.R.China

Cyrus Tang Hematology Center,Collaborative Innovation Center of Hematology,Soochow University,National Clinical Research Center for Hematologic Diseases,The First Affiliated Hospital of Soochow University,State Key Laboratory of Radiation Medicine and Protection,Soochow University,Suzhou 215123,P.R.China

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出版年：

2024

DOI：

10.1038/s41392-024-02013-w

信号转导与靶向治疗(英文)

CSTPCD

ISSN：

年,卷(期)：2024.9(12)