Autophagy. 2025 Dec 31.
Endoplasmic reticulum (ER) exit sites (ERES) serve as essential hubs for the packaging and export of secretory proteins into the COPII vesicular pathway. Previous studies have shown that ERES are dynamic and capable of adapting to stress, but the molecular details controlling their degradation under nutrient stress conditions were largely unknown. The study by Liao et al. (2024) introduces a new mechanism in which ERES are degraded through lysosome-dependent microautophagy in response to nutrient stress. This process is uniquely facilitated by COPII components, the calcium-binding adaptor ALG2, and the ESCRT machinery. The authors demonstrate that inhibiting MTOR triggers calcium release from lysosomes, which then recruits ALG2, leading to SEC31 ubiquitination and subsequently promoting PDCD6IP/ALIX-ESCRT-dependent lysosomal engulfment of ERES. This research reveals an unexplored pathway for the quality control and recycling of secretory machinery, thereby improving our understanding of ER turnover and establishing a mechanistic link between nutrient sensing, autophagy, and remodeling of the secretory pathway.
Keywords: Autophagy; COPII; ESCRT; er exit sites; microautophagy