Step-by-step process of bringing ULK1 protein to membranes during cell cleanup

The autophagy-initiating complex ULK1C involves a critical interaction with the PI3P-binding protein WIPI3.

• The ATG13:ATG101 dimer interacts with WIPI2 and WIPI3, facilitating complex formation on membranes.
• Molecular dynamics simulations indicate that WIPIs and the WF finger enhance stability of the complex on membranes.
• Engagement of WIPI3 with ATG13 promotes phosphorylation of ATG16L1, which is linked to autophagy and mitophagy.
• The PVP motif in ULK1's disordered region is necessary for its phosphorylation of ATG16L1 in vitro.
• The findings suggest a specific pathway for recruiting ULK1 to membrane surfaces, essential for autophagy processes.

Simplified