Biomolecular condensates and disease pathogenesis  

作　　者：Ke Ruan Ge Bai Yanshan Fang Dan Li Tingting Li Xingguo Liu Boxun Lu Qing Lu Zhou Songyang Shuguo Sun Zheng Wang Xin Zhang Wen Zhou Hong Zhang 

机构地区：[1]The First Affiliated Hospital&School of Life Sciences,Ministry of Education Key Laboratory for Membrane-less Organelles&Cellular Dynamics,Hefei National Research Center for Interdisciplinary Sciences at the Microscale,Center for Advanced Interdisciplinary Science and Biomedicine of IHM,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230027,China [2]Nanhu Brain-computer Interface Institute,Hangzhou 311100,China [3]Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine,Zhejiang University School of Medicine,Hangzhou 310058,China [4]Interdisciplinary Research Center on Biology and Chemistry,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai 201210,China [5]University of Chinese Academy of Sciences,Beijing 100049,China [6]Bio-X Institutes,Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education),Shanghai Jiao Tong University,Shanghai 200030,China [7]Department of Biomedical Informatics,School of Basic Medical Sciences,Peking University Health Science Center,Beijing 100191,China [8]CAS Key Laboratory of Regenerative Biology,Joint School of Life Sciences,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou 510530,China [9]Joint School of Life Sciences,Guangzhou Medical University,Guangzhou 510000,China [10]Neurology Department at Huashan Hospital,State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science,Institutes of Brain Science,School of Life Sciences,Fudan University,Shanghai 200433 China [11]Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders,Ministry of Education,Bio-X Institutes,Shanghai Jiao Tong University,Shanghai 200030,China [12]State Key Laboratory of Biocontrol,MOE Key Laboratory of Gene Function and Regulation and Guangzhou Key Laboratory of Healthy Aging Research,School of Life Sciences,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510275

出　　处：《Science China(Life Sciences)》2024年第9期1792-1832,共41页中国科学（生命科学英文版）

基　　金：supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0480000);the National Key Research and Development Program of China(2022YFA1103800,2022YFA1303100,2023YFE0210100);the National Natural Science Foundation of China(22337005,22377119,32025010,32241002,32270812,32270920,32325016,32350024,32261160376,82150003,82188101,82325016,92157202,92254301,T2325003);STI2030-Major Projects(2021ZD0202501);the Science and Technology Commission of Shanghai Municipality(2019SHZDZX02,20490712600);the Key Research Program CAS(ZDBS-ZRKJZ-TLC003);International Cooperation Program CAS(154144KYSB20200006);CAS Project for Young Scientists in Basic Research(YSBR-075);Guangdong Province Science and Technology Program(2023B1111050005,2023B1212060050);Natural Science Foundation of Anhui Province(2108085J12);Center for Advanced Interdisciplinary Science and Biomedicine of IHM(QYPY20220008);Shenzhen Talent Program(KQTD20210811090115021);Guangdong Innovative and Entrepreneurial Research Team Program(2021ZT09Y104)。

摘　　要：Biomolecular condensates or membraneless organelles(MLOs)formed by liquid-liquid phase separation(LLPS)divide intracellular spaces into discrete compartments for specific functions.Dysregulation of LLPS or aberrant phase transition that disturbs the formation or material states of MLOs is closely correlated with neurodegeneration,tumorigenesis,and many other pathological processes.Herein,we summarize the recent progress in development of methods to monitor phase separation and we discuss the biogenesis and function of MLOs formed through phase separation.We then present emerging proof-of-concept examples regarding the disruption of phase separation homeostasis in a diverse array of clinical conditions including neurodegenerative disorders,hearing loss,cancers,and immunological diseases.Finally,we describe the emerging discovery of chemical modulators of phase separation.

关 键 词：liquid-liquid phase separation biomolecular condensate membraneless organelle 

分 类 号：R363[医药卫生—病理学]