The dynamic and heterogeneous composition of biomolecular condensates and its functional relevance

Biomolecular condensates are non-membrane-encapsulated compartments that control various biological processes, largely by enriching and excluding certain molecules. Emerging evidence demonstrates that condensate compositions dynamically change in response to stimuli and over time. Thus, condensates that share a designation and general function can substantially vary in their composition. In this Review, we discuss the current understanding of condensate composition changes and heterogeneity, how they are regulated and how the changes affect biochemical reactions. We focus on four condensates: DNA double-strand break (DSB) repair foci, promyelocytic leukaemia (PML) nuclear bodies, processing bodies (P-bodies) and RNA transport granules, with examples from stress granules and germ granules. Changes in condensate composition seem to support complex reactions, such as those occurring in DNA repair and RNA processing. Mechanisms regulating composition changes include biophysical features of components, modifications, nodes and enzymatic reactions. We also speculate about the impact of protein mislocalization and mutations on condensate composition and function, including in cancer and neurodegenerative diseases. We conclude by discussing outstanding questions and the implications of studying condensate composition changes for research and therapeutics.