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

Phase separation and transition control the assembly and material states (liquid, gel like, or solid) of protein condensates to ensure that distinct cellular functions occur in a spatiotemporally controlled manner. The assembly and biophysical properties of condensates are precisely regulated by chaperone proteins, post-translational modifications (PTMs), and numerous cellular factors. Phase separation also triages misfolded and unwanted proteins for autophagic degradation. The concerted actions of receptor proteins, scaffold proteins, and PTMs determine the size, assembly rate, and material properties of condensates for efficient removal. Altered phase separation and transition affect the degradation of protein condensates, resulting in their accumulation under certain developmental and pathological conditions. Elucidation of the role of phase separation and transition in the degradation of disease-related protein condensates will provide insights into the molecular mechanism underlying the pathogenesis of various diseases.