Phase Separation, Transition, and Autophagic Degradation of Proteins in Development and Pathogenesis

Protein condensates are assembled via phase separation and exhibit distinct material properties (e.g., liquid, gel-like, or solid state). The biophysical properties of protein condensates are important for their distinct cellular functions. The liquid-to-amyloid-like fibrillization of protein condensates is prevented by chaperones such as HSP70 and TNPO1 and facilitated by protein mutations and by cosegregation of misfolded proteins. The aberrant solid-state transition of protein condensates is associated with the pathogenesis of various diseases. Receptor proteins, scaffold proteins, and PTMs control the size, formation rate, and biophysical properties of phase-separated protein condensates, which in turn determine their autophagic degradation or accumulation under various developmental conditions