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 ph...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.展开更多
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)+10 种基金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)。
文摘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.