Wetting regulates autophagy of phase-separated compartments and the cytosol

While the importance of compartmentalization of cellular material in droplet-like structures is increasingly recognized, the mechanisms of droplet removal are still poorly understood. Evidence suggests that droplets can be degraded by autophagy, a degradation system in which membrane sheets bend to isolate portions of the cytoplasm within double-membrane vesicles known as autophagosomes. Here, we examine how autophagosomes sequester droplets that contain the protein p62 in living cells, and also demonstrate that autophagosome-like vesicles form at the surface of protein-free droplets through partial wetting in an in-vitro system. Using a minimal physical model, we show that droplet surface tension supports the formation of membrane sheets, in a manner robust to variations in the droplet-membrane interaction strength. Furthermore, we uncover a switching mechanism that allows droplets to act either as autophagy targets, or as liquid assembly platforms for the formation of cytosol-degrading autophagosomes. All in all, droplet-mediated autophagy belongs to a novel class of intracellular processes that are driven by elastocapillarity and highlight the importance of wetting in cytosolic organization.