Oral Presentation 11th International Symposium on Autophagy 2025

Critical roles of ER phagy receptors in autophagosome biogenesis (128636)

Chunmei Chang 1
  1. Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China

A fundamental event in selective autophagy is the formation of the double-membrane vesicle known as autophagosome at designated cargos. In mammalian cells, a set of core autophagy machinery coordinate various reactions needed to generate autophagosomes. Recent advances highlight the critical roles of cargo receptors in the initiation of selective autophagy pathways. In our previous studies, we reconstituted a set of the key sub-circuits of the autophagosome biogenesis process, and established a start-to-finish reconstitution of mitophagy initiation from the receptor engagement through LC3 lipidation. Here, using a combination of in vitro reconstitution, structural modeling and cell biology, we find that the ER membrane resident receptors directly engage with distinct core autophagy machinery. By characterizing these interactions, we demonstrate that the ER phagy receptors play critical roles in both the initiation and expansion stages of ER autophagosome formation.