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Mechanisms and regulation underlying membraneless organelle plasticity control
Hazrat Ismail1 , Xu Liu1,2 , Fengrui Yang1,2 , Junying Li1,3 , Ayesha Zahid1 , Zhen Dou1 , Xing Liu1,3,* , Xuebiao Yao1,3,*
1MOE Key Laboratory for Membraneless Organelles & Cellular Dynamics and CAS Center for Excellence in Molecular Cell Science, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230027, China
2Keck Center for Organoids Plasticity Control, Atlanta, GA 30310, USA
3Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, Hefei 230027, China
*Correspondence to:Xing Liu , Email:xing1017@ustc.edu.cn Xuebiao Yao , Email:yaoxb@ustc.edu.cn
J Mol Cell Biol, Volume 13, Issue 4, April 2021, Pages 239-258  https://doi.org/10.1093/jmcb/mjab028
Keyword: liquid–liquid phase separation, membraneless organelles, biomolecular condensates, intrinsically disordered proteins, post-translational modifications

Evolution has enabled living cells to adopt their structural and functional complexity by organizing intricate cellular compartments, such as membrane-bound and membraneless organelles (MLOs), for spatiotemporal catalysis of physiochemical reactions essential for cell plasticity control. Emerging evidence and view support the notion that MLOs are built by multivalent interactions of biomolecules via phase separation and transition mechanisms. In healthy cells, dynamic chemical modifications regulate MLO plasticity, and reversible phase separation is essential for cell homeostasis. Emerging evidence revealed that aberrant phase separation results in numerous neurodegenerative disorders, cancer, and other diseases. In this review, we provide molecular underpinnings on (i) mechanistic understanding of phase separation, (ii) unifying structural and mechanistic principles that underlie this phenomenon, (iii) various mechanisms that are used by cells for the regulation of phase separation, and (iv) emerging therapeutic and other applications.