Driven molecular fluxes control the size of an essential phase-separated organelle in algae

Synopsis

Liquid-liquid phase separation has emerged as an important mechanism by which cells organize molecules and organelles. Investigating the physical principles by which these biomolecular condensates facilitate cellular functions, which are generically out-of-equilibrium, remains a grand challenge at the intersection of statistical physics and cell biology. The inherent out-of-equilibrium nature and complexity of biological systems has posed a significant obstacle to conceptual progress in this field. We leverage the algal pyrenoid—an experimentally tractable condensate responsible for 30% of global CO2 fixation—as a powerful model system. During cell division, the liquid-liquid phase separated pyrenoid undergoes rapid dissolution and recondensation. We identify a kinase, KEY1, that regulates pyrenoid dissolution by phosphorylation and proves to be essential for controlling out-of-equilibrium dynamics to stabilize pyrenoid number, size, and function. We develop a minimal mathematical model of kinase activity that recapitulates the dynamic behaviors seen in vivo and suggests how molecular fluxes driven by kinase activity can robustly control condensate formation and localization.