Phase Separation in Regulation of Aggrephagy

The selective degradation of protein aggregates is called aggrephagy. Misfolded proteins are thought to form aggregates, which are then surrounded by selective autophagy receptors and targeted to autophagosomes for degradation. Recent studies of p62 bodies, PGL granules, and stress granules indicate that proteins targeted for aggrephagy are not simple protein aggregates but rather form liquid-like protein condensates through liquid–liquid phase separation. The liquid-like properties of the condensates and hardening to a gel-like state may be crucial in the initiation of aggrephagy. Dysregulation of phase separation may cause human diseases. Here we review the potential roles of liquid–liquid phase separation in the process of aggrephagy. [Display omitted] •p62 body, PGL granule and aberrant stress granule formed through phase separation.•Multivalent interactions between p62 and poly-Ubiquitin drive p62 body formation.•PGL granules in somatic cells formed through PGL-1 and PGL-3 phase separation•Phase transition of stress granule triggers its degradation through autophagy.•Liquid-like properties of the condensates are crucial in the initiation of aggrephagy.