Reciprocal regulation of phase separation and cellular metabolism. (a) Hypoxia induces condensation of glycolytic enzymes into ‘G bodies’. G bodies promote cycling through the entire glycolytic pathway, reflected by increased levels of glucose-6-phosphate, fructose-6-phosphate and fructose-1,6-bisphosphate, and decreased levels of acetyl-CoA. Under normoxia, glycolytic enzymes remain diffusive in the cytoplasm. Starvation induces filament formation of glutamine synthetase (Gln1) and promotes its inactivation and storage in the cytoplasm. In the presence of nutrients, Gln1 is evenly distributed through the cytoplasm. (b) In response to growth signals, mTORC1 (blue) tunes macromolecular crowding by modulating ribosome concentration (grey) in the cytoplasm. Higher crowding favors phase separation and molecular assembly. In the absence of growth signals, ribosome concentration is decreased by ribophagy. glucose-6P, glucose-6-phosphate; fructose-6P, fructose-6-phosphate; fructose-1,6-biP, fructose-1,6-bisphosphate; acetyl-CoA, acetyl coenzyme-A; α-KG, α-ketoglutarate; SFP1, transcription factor SFP1.