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. Author manuscript; available in PMC: 2023 Jan 21.
Published in final edited form as: Mol Cell. 2022 Mar 31;82(8):1501–1513. doi: 10.1016/j.molcel.2022.03.012

Figure 3. Model for in situ autophagosome nucleation.

Figure 3.

(A) Early models for selective autophagy posited that LIR motifs within cargo receptors associate with ATG8 proteins on pre-existing phagophores, generated by the action of ULK1, VPS34, lipidation, and WIPI complexes.

(B) In newly emerging models for autophagosome nucleation, cargo receptors directly associate with the FIP200 component of the ULK1 complex, including through a FIR/LIR-claw domain interaction, to initiate autophagosome assembly adjacent to the surface of the target cargo. Receptor-ULK1 complexes can be recruited either via galectins in association with glycans or via ubiquitylated cargo. As ATG8 becomes conjugated to the growing phagophore, ATG8 proteins can subsequently bind to LIR motifs in cargo receptors to ensure cargo capture and autophagosome maturation in proximity to the target surface.