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.

脂滴（LD）是动态的脂质储存细胞器，可以被自噬机制降解以释放中性脂质，这一过程称为脂肪自噬。然而，脂肪吞噬的具体受体和调节机制仍然很大程度上未知。在这里，我们确定 PI3KC3-C1 复合物的核心单元 ATG14 也以 LD 为目标，并充当促进 LD 降解的自噬受体。 Syntaxin18 (STX18) 是一种负调节因子，可结合 ATG14，破坏 ATG14-ATG8 家族成员的相互作用并破坏 PI3KC3-C1 复合物的形成。 STX18 的敲低会激活依赖于 ATG14 的脂质自噬，ATG14 不仅作为 PI3KC3-C1 复合物的核心单元，而且作为自噬受体，导致 LD 相关抗病毒蛋白 Viperin 的降解。此外，冠状病毒M蛋白结合STX18并破坏STX18-ATG14相互作用，诱导脂肪自噬并降解Viperin，促进病毒产生。总而言之，我们的数据为 ATG14 在脂质代谢和病毒产生中的其他作用提供了一种先前未描述的机制。