Editorial Cite This: Biochemistry 2018, 57, 2403−2404
pubs.acs.org/biochemistry
Special Issue on Membraneless Organelles
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be fully functional, cells must dynamically regulate assembly as well as disassembly, which is discussed in the Perspective by Ashok Deniz (The Scripps Research Institute). Xiao-Han Li and Madan Babu (University of Cambridge) explore how cells use biological condensates to optimize fitness and respond to changes such as stress.
ll biological systems use location as a determinant of function at different scales, ranging from whole organisms to atoms within biomolecules. How to get key actors to the right locations at the right time and how to keep them there until they are no longer needed are key logistical challenges cells must perfect in order to thrive. Cells use different strategies to regulate localization; the best known is compartmentalization into traditional membrane-bound organelles such as the nucleus, endoplasmic reticulum, or Golgi complex. In the past few years, it has been proposed that membraneless organelles exist and complement larger classical organelles. This special issue will explore this exciting new concept. It has long been a mystery how the cell organizes itself within a tightly packed interior to achieve processes that are not constrained within classical organelles. A new model proposes that biological molecules form condensates through liquid− liquid phase transitions and self-organize into membraneless organelles. The concept of phase transitions is familiar within membranes, for example, through the formation of lipid rafts or other microdomains. Compartmentalization through liquid− liquid phase transitions is an attractive idea, and numerous groups are working to better understand its biological significance. The discovery of membraneless organelles, exploring their significance, and providing a theoretical framework to study them systematically are prime examples for modern multidisciplinary research. The field draws on a broad range of disciplines, including engineering, biological chemistry, biophysics, systems biology, computational biology, and cell biology. At Biochemistry we are in the process of expanding the scope of the journal to cover biological chemistry research in the broadest sense, and as such we are delighted to host this special issue.
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PROPOSED BIOLOGICAL ROLES OF MEMBRANELESS ORGANELLES Biological condensates have been suggested to be involved in a growing list of biological structures and functions. Many of these involve interactions between proteins and nucleic acids, suggesting that the physical properties of these systems are particularly suited for liquid−liquid phase transitions. The Perspective by Karla Neugebauer (Yale University) focuses on nuclear bodies, including the nucleolus, Cajal bodies, and histone locus bodies; Sarah Slavoff (Yale University) and Graciela Boccaccio (Fundación Instituto Leloir, Buenos Aires) discuss P bodies and stress granules, respectively. An article by Nicolas Fawzi (Brown University) reports interactions between low-complexity proteins and RNA polymerase. Philip Bevilacqua and Christine Keating (The Pennsylvania State University) focus on possible liquid−liquid phase separations involving RNA during the origins of life, and Geeta Narlikar (University of California, San Francisco) suggests that heterochromatin has liquid droplet-like properties. Finally, Mingjie Zhang (Hong Kong University of Science and Technology) discusses the role of phase separation during synaptic assembly.
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EXPLAINING AND UNDERSTANDING THE THEORY OF LIQUID−LIQUID PHASE TRANSITIONS In broad introductions to the topic, Alex Holehouse and Rohit Pappu (Washington University in St. Louis) define and explain concepts underlying phase transitions and possible functional consequences, and Daniel Jarosz (Stanford University) explores potential mechanisms of regulation. Liquid−liquid phase transitions are familiar to polymer chemists and physicists, and the conceptual frameworks from these fields can be applied to biological assemblies. Intrinsically disordered proteins are particularly suitable to such analyses, which are discussed by Erik Martin and Tanja Mittag (St. Jude Children’s Research Hospital) as well as Julie Forman-Kay and Hue Sun Chan (University of Toronto). Ashutosh Chilkoti (Duke University) draws analogies between the phase behavior of artificial protein polymers and low-complexity proteins. While most analyses focus on the roles of proteins or other biomolecules such as RNA, Boris Zaslavsky (Cleveland Diagnostics) and Vladimir Uversky (University of South Florida) highlight the importance of water in phase separation. For membraneless organelles to © 2018 American Chemical Society
OUTLOOK
The field of membraneless organelles is expanding rapidly, with several recent biological observations reported. Many of these are reviewed in this special issue and, together with theoretical analyses, provide intriguing hints that a new organizational principle has been uncovered. The next challenge in this area is to discover clear evidence that these putative new localization hubs are actively created and maintained by cells. Researchers are taking an array of approaches toward this goal. For example, Jared Toettcher (Princeton University) discusses how optogenetics can be used to manipulate the separation of proteins into different assemblies.
Ulrike S. Eggert,* Associate Editor, Biochemistry
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Randall Centre for Cell and Molecular Biophysics and Department of Chemistry, King’s College London, London, U.K.
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. Special Issue: Membrane-Less Organelles Published: May 1, 2018 2403
DOI: 10.1021/acs.biochem.8b00428 Biochemistry 2018, 57, 2403−2404
Biochemistry
Editorial
ORCID
Ulrike S. Eggert: 0000-0003-0932-5525 Notes
Views expressed in this editorial are those of the author and not necessarily the views of the ACS.
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DOI: 10.1021/acs.biochem.8b00428 Biochemistry 2018, 57, 2403−2404
