@article {69351,
	title = {COPII with ALG2 and ESCRTs control lysosome-dependent microautophagy of ER exit sites.},
	journal = {Dev Cell},
	year = {2024},
	month = {2024 Apr 06},
	abstract = {<p>Endoplasmic reticulum exit sites (ERESs) are tubular outgrowths of endoplasmic reticulum that serve as the earliest station for protein sorting and export into the secretory pathway. How these structures respond to different cellular conditions remains unclear. Here, we report that ERESs undergo lysosome-dependent microautophagy when Ca\&nbsp;is released by lysosomes in response to nutrient stressors such as mTOR inhibition or amino acid starvation in mammalian cells. Targeting and uptake of ERESs into lysosomes were observed\&nbsp;by\&nbsp;super-resolution live-cell imaging and focus ion beam scanning electron microscopy (FIB-SEM). The mechanism\&nbsp;was ESCRT dependent and required\&nbsp;ubiquitinated SEC31, ALG2, and ALIX, with a knockout of ALG2 or function-blocking mutations of ALIX preventing engulfment of ERESs by lysosomes. In\&nbsp;vitro, reconstitution of the pathway was possible using lysosomal lipid-mimicking giant unilamellar vesicles and purified recombinant components. Together, these findings demonstrate a pathway of lysosome-dependent ERES microautophagy mediated by COPII, ALG2, and ESCRTS induced by nutrient stress.</p>
},
	issn = {1878-1551},
	doi = {10.1016/j.devcel.2024.03.027},
	author = {Liao, Ya-Cheng and Pang, Song and Li, Wei-Ping and Shtengel, Gleb and Choi, Heejun and Schaefer, Kathy and Xu, C Shan and Lippincott-Schwartz, Jennifer}
}
