Biomolecular condensates—Prerequisites for anhydrobiosis?

It is often underappreciated that despite water being a requirement for life on Earth, organisms belonging to all taxonomic kingdoms have developed mechanisms to survive desiccation. These organisms, referred to as anhydrobiotes, accumulate specific biomolecules during or before drying that facilitate the survival of desiccation stress. Compounds utilized by a wide variety of anhydrobiotes during desiccation include metabolites such as sugars and amino acids, as well as proteins with extensive intrinsically disordered regions. Intrinsically disordered proteins that are constitutively expressed or upregulated during the onset or in preparation for desiccation include late embryogenesis abundant proteins, tardigrade disordered proteins, hydrophilins, some small heat shock proteins, and prion-like proteins. Some of these proteins form biomolecular condensates in the cellular environment. We hypothesize that phase transitions driven by anhydrobiosis-related intrinsically disordered proteins play a substantial role in enabling anhydrobiosis by (1) contributing to the downregulation of metabolic and developmental processes, (2) selectively sequestering desiccation-sensitive molecules into a “protective compartment” during drying, (3) interfering with programmed cell death signaling pathways to confer optimal time for the cell to repair after rehydration, (4) resisting intracellular volume changes to aid in membrane stabilization during desiccation, and (5) changing the biophysical properties of water to reduce desiccation-induced cellular damage. Biochemical strategies in anhydrobiotes are certainly multifaceted and may differ among systems. Nevertheless, a better understanding of the relevance of phase transitions in anhydrobiosis may allow us to get one step closer to unraveling the enigmatic phenomenon of life without water.