COPII with ALG2 and ESCRTs control lysosome-dependent microautophagy of ER exit sites.
Dev Cell
; 59(11): 1410-1424.e4, 2024 Jun 03.
Article
de En
| MEDLINE
| ID: mdl-38593803
ABSTRACT
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 Ca2+ 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 by super-resolution live-cell imaging and focus ion beam scanning electron microscopy (FIB-SEM). The mechanism was ESCRT dependent and required ubiquitinated SEC31, ALG2, and ALIX, with a knockout of ALG2 or function-blocking mutations of ALIX preventing engulfment of ERESs by lysosomes. In 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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Protéines de liaison au calcium
/
Vésicules COP
/
Protéines du transport vésiculaire
/
Réticulum endoplasmique
/
Complexes de tri endosomique requis pour le transport
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Microautophagie
/
Lysosomes
Limites:
Humans
Langue:
En
Journal:
Dev Cell
Sujet du journal:
EMBRIOLOGIA
Année:
2024
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique