Autophagy, an essential process in eukaryotic cells, entails the sequestration and degradation of cytosolic components and organelles following fusion with the lysosome or vacuole. Autophagy-related protein 18 (Atg18), a key autophagy-related protein, binds phosphatidylinositol-3-phosphate (PI3P) to localize to autophagosomal membranes, where it recruits Atg2 to mediate lipid transfer during autophagosome biogenesis. Although the roles of Atg18 in autophagy are well established, whether this protein exerts additional regulatory functions in this process remains to be elucidated. Here, we report the weak interactions between Atg18 and Atg8 or Atg16 mediated by the Atg8-interacting motif (AIM) within Atg18. Disruption of the AIM in Atg18 leads to reduced autophagosome formation and diminished autophagic activity. Moreover, we demonstrate that Atg18 is involved in the recruitment of Atg8 to the autophagosome and facilitates the C-terminal cleavage of Atg8 by Atg4. Furthermore, the Atg18-Atg8 complex can be dissociated by Atg3, enabling free Atg18 to subsequently recruit Atg16 to the autophagosome, preparing for Atg8 lipidation. Thus, our findings unveil previously unknown roles for Atg18 in downstream factor recruitment and Atg4 cleavage during autophagosome formation via its AIM.

• PMID: 40956874
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Journal Article

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Li T, Li X, Li M, Yuan T, Ma C

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