Abstract
AbstractLipid 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.
Funder
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary