Active regulation mechanisms of LLPS and MLOs biogenesis

Biocondensates are found in the nucleus and the cytosol and associated to cellular membranes. They form when the local concentration of biomolecules increases above saturation levels. The cytosolic crowding limits the movement of biomolecules to the sites of condensation, and membrane-less organelle (MLO) formation may involve active transport by molecular motors. Dynein, kinesin, and myosin govern the dynamic assembly of stress granules (SGs) and P-bodies (PBs). Liquid–liquid phase separation is controlled by biochemical modifications of RNA and protein molecules. RNA methylation contributes to the assembly of SGs. The covalent linkage of PAR or SUMO chains increases the number of intermolecular contacts between proteins and promotes their demixing. RNA and PAR chains increase the fluidity of the separated phase. PBs, Smaug-bodies, Pumilio-bodies, and other MLOs that contain mRNAs and regulate translation respond to diverse stimuli, from synapse activation to nutrient sensing. The mTOR/AMPK pathway controls several cellular condensates involved in diverse functions, including autophagy, glycolysis, and translational regulation.