Roles of phase separation and condensates in autophagy

Autophagy is an intracellular degradation process conserved among eukaryotes, which contributes to cellular homeostasis through the degradation of not only proteins but also organelles and invasive microbes. A hallmark feature of autophagy is the de novo generation of a double-membrane organelle known as an autophagosome, which sequesters diverse cytoplasmic materials and delivers them to a lysosome (a vacuole in yeast and plants) for degradation. Autophagosome formation is mediated by approximately 20 autophagy-related (Atg) proteins that have been, in principle, conserved throughout evolution. Recent studies unveiled two distinct roles of liquid–liquid phase separation (LLPS) in autophagy: one regulates Atg proteins and the other regulates autophagy substrates. In this chapter, the roles of LLPS in autophagy are summarized as well as the significance of the physicochemical properties of phase-separated condensates in the regulation of membrane dynamics during autophagy.