BioAcyl Corp

(A) Macromolecules, including proteins, RNAs, and other cellular components are dispersed throughout the cytosol. (B) Macromolecule crowding leads to cargo formation through two mechanisms: (i) intrinsic cellular processes and protein-intrinsic factors, or (ii) autophagy receptors that actively induce crowding of cargo molecules. Both processes result in the formation of a phase-separated structure that can be targeted for degradation. (C) Cargo receptors and early autophagy factors can phase-separate on the cargo surface and promote the formation of phase-separated initiation hubs. (D) Initiation hubs, that diffuse on the cargo surface, coalesce at a single location near specific endoplasmic reticulum (ER) subdomains or the vacuole, leading to the formation of the phagophore assembly site (PAS). (E) The phagophore nucleates from the PAS, and the cargo and the phagophore interact through wetting.