ATG14 targets lipid droplets and acts as an autophagic receptor for syntaxin18-regulated lipid droplet turnover
Zhen Yuan,
Kun Cai,
Jiajia Li,
Ruifeng Chen,
Fuhai Zhang,
Xuan Tan,
Yaming Jiu,
Haishuang Chang,
Bing Hu,
Weiyi Zhang and
Binbin Ding ()
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Zhen Yuan: Huazhong University of Science and Technology
Kun Cai: Hubei Provincial Center for Disease Control and Prevention
Jiajia Li: Huazhong University of Science and Technology
Ruifeng Chen: Huazhong University of Science and Technology
Fuhai Zhang: Huazhong University of Science and Technology
Xuan Tan: Huazhong University of Science and Technology
Yaming Jiu: Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences
Haishuang Chang: Shanghai Jiaotong University School of Medicine
Bing Hu: Hubei Provincial Center for Disease Control and Prevention
Weiyi Zhang: Dong-A University
Binbin Ding: Huazhong University of Science and Technology
Nature Communications, 2024, vol. 15, issue 1, 1-18
Abstract:
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.
Date: 2024
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DOI: 10.1038/s41467-024-44978-w
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