Autophagy, 15 January, 2024, DOI：https://doi.org/10.1080/15548627.2024.2317116

Reticulophagy mediated by the V-ATPase-ATG16L1-LC3C axis

Yiwei Sun & Xi Wang

Abstract

The lysosomal degradation of the endoplasmic reticulum (ER), known as “reticulophagy”, is important for protein quality control and organelle turnover. Here we present a noncanonical reticulophagy occurring at ER exit sites (ERESs) induced by the misfolded SERPINA1/α1-antitrypsin (AAT) mutant, Z-AAT. The accumulation of Z-AAT arrests ER-to-Golgi transport, and recruits V-ATPase and ATG16L1 to mediate LC3C decoration of ERESs. Consequently, the receptor RETREG1/FAM134B–2 is recruited by lipidated LC3C to initiate reticulophagy. Furthermore, the blockade of ER export acts as a universal signal to activate reticulophagy mediated by the V-ATPase-ATG16L1-LC3C axis. This study sheds light on the mechanism of how ERESs switch from ER export to reticulophagy for quality control.

Article link：https://www.tandfonline.com/doi/full/10.1080/15548627.2024.2317116