ATG14 targets lipid droplets and acts as an autophagic receptor for syntaxin18-regulated lipid droplet turnover.
Nat Commun
; 15(1): 631, 2024 Jan 20.
Article
em En
| MEDLINE
| ID: mdl-38245527
ABSTRACT
Lipid droplets (LDs) are dynamic lipid storage organelles that can be degraded by autophagy machinery to release neutral lipids, a process called lipophagy. However, specific receptors and regulation mechanisms for lipophagy remain largely unknown. Here, we identify that ATG14, the core unit of the PI3KC3-C1 complex, also targets LD and acts as an autophagic receptor that facilitates LD degradation. A negative regulator, Syntaxin18 (STX18) binds ATG14, disrupting the ATG14-ATG8 family members interactions and subverting the PI3KC3-C1 complex formation. Knockdown of STX18 activates lipophagy dependent on ATG14 not only as the core unit of PI3KC3-C1 complex but also as the autophagic receptor, resulting in the degradation of LD-associated anti-viral protein Viperin. Furthermore, coronavirus M protein binds STX18 and subverts the STX18-ATG14 interaction to induce lipophagy and degrade Viperin, facilitating virus production. Altogether, our data provide a previously undescribed mechanism for additional roles of ATG14 in lipid metabolism and virus production.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metabolismo dos Lipídeos
/
Gotículas Lipídicas
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2024
Tipo de documento:
Article