Biomolecular condensates in neurodegeneration and cancer

• Published in: Traffic (Copenhagen, Denmark) Vol. 20; no. 12; pp. 890 - 911
• Main Authors: Spannl, Stephanie, Tereshchenko, Maria, Mastromarco, Giovanni J., Ihn, Sean J., Lee, Hyun O.
• Format: Journal Article
• Language: English
• Published: Former Munksgaard John Wiley & Sons A/S 01.12.2019; Wiley Subscription Services, Inc
• Subjects: biomolecular condensates; cancer; Condensates; disease; membrane‐less organelles; Neurodegeneration; Organelles; phase separation; phase transition; Prokaryotes; phase separation; disease; neurodegeneration; cancer; phase transition; biomolecular condensates; membrane-less organelles
• ISSN: 1398-9219; 1600-0854; 1600-0854
• DOI: 10.1111/tra.12704

The intracellular environment is partitioned into functionally distinct compartments containing specific sets of molecules and reactions. Biomolecular condensates, also referred to as membrane‐less organelles, are diverse and abundant cellular compartments that lack membranous enclosures. Molecules assemble into condensates by phase separation; multivalent weak interactions drive molecules to separate from their surroundings and concentrate in discrete locations. Biomolecular condensates exist in all eukaryotes and in some prokaryotes, and participate in various essential house‐keeping, stress‐response and cell type‐specific processes. An increasing number of recent studies link abnormal condensate formation, composition and material properties to a number of disease states. In this review, we discuss current knowledge and models describing the regulation of condensates and how they become dysregulated in neurodegeneration and cancer. Further research on the regulation of biomolecular phase separation will help us to better understand their role in cell physiology and disease. Cellular space is divided into discrete compartments containing distinct sets of molecules. This review focuses on a group of evolutionarily conserved compartments called biomolecular condensates. Condensates lack membrane enclosures and instead concentrate molecules via phase separation; molecules demix from their surroundings through multivalent weak interactions to form separate phases. We highlight current knowledge and models describing the regulation of condensates implicated in neurodegeneration and cancer. Further studies in their regulation will provide important insight into these diseases.