Phase separation of initiation hubs on cargo is a trigger switch for selective autophagy

Licheva M, Pflaum J, Babic R, Manchilla H, Elsässer J, Boyle M, Hollenstein DM, Jimenez-Niebla J, Pleyer J, Heinrich M, Wieland FG, Brenneisen J, Eickhorst C, Brenner J, Jiang S, Hartl M, Welsch S, Hunte C, Timmer J, Wilfling F, Kraft C

Nat Cell Biology 2025; DOI: https://doi.org/10.1038/s41556-024-01572-y

Autophagy ensures cellular quality control. Phase separation of key factors at cargo surfaces forms dynamic initiation hubs for membrane nucleation. Weak receptor-cargo binding enable selective degradation, while strong binding inhibits it, highlighting the importance of regulated phase separation.