ATG14, short for autophagy-related 14, is a key regulator in autophagy. It is an essential component for the fusion of autophagosomes with lysosomes, a crucial step in the autophagy-lysosomal degradation system. Autophagy is a cellular process involved in maintaining cellular homeostasis, and ATG14-regulated autophagy is linked to various biological processes such as lipid metabolism and inflammation regulation [1,2,3,4].

In macrophages of human and mouse atherosclerotic plaques, reduced ATG14 expression leads to impaired autophagy function. Overexpressing ATG14 in macrophages enhances autophagosome-lysosome fusion, promotes lipid degradation, and alleviates atherosclerotic lesions by inhibiting inflammation and upregulating Treg cells [1]. In hepatocytes, ATG14 is enriched on lipid droplets. Its deficiency decreases triglyceride hydrolysis, suggesting it directly enhances lipid droplet breakdown through interactions with ATGL and CGI-58 [3]. Also, in the context of coronavirus, ATG14 acts as an autophagic receptor for lipid droplet turnover. Syntaxin18 (STX18) negatively regulates this process, and coronavirus M protein can hijack STX18-ATG14 axis-regulated lipophagy to evade an anti-viral effect [2,4].

In summary, ATG14 plays essential roles in autophagy-related processes such as autophagosome-lysosome fusion and lipid metabolism. The study of ATG14 using gene knockout models in mice has provided valuable insights into its role in diseases like atherosclerosis and viral infections, highlighting its potential as a therapeutic target.

References:

1. Zhang, Hui, Ge, Song, Ni, Buqing, Wu, Xiaohong, Shao, Yongfeng. 2021. Augmenting ATG14 alleviates atherosclerosis and inhibits inflammation via promotion of autophagosome-lysosome fusion in macrophages. In Autophagy, 17, 4218-4230. doi:10.1080/15548627.2021.1909833. https://pubmed.ncbi.nlm.nih.gov/33849389/

2. Yuan, Zhen, Cai, Kun, Li, Jiajia, Zhang, Weiyi, Ding, Binbin. 2024. ATG14 targets lipid droplets and acts as an autophagic receptor for syntaxin18-regulated lipid droplet turnover. In Nature communications, 15, 631. doi:10.1038/s41467-024-44978-w. https://pubmed.ncbi.nlm.nih.gov/38245527/

3. Huang, Menghao, Zhang, Yang, Park, Jimin, Yu, Liqing, Dong, X Charlie. 2023. ATG14 plays a critical role in hepatic lipid droplet homeostasis. In Metabolism: clinical and experimental, 148, 155693. doi:10.1016/j.metabol.2023.155693. https://pubmed.ncbi.nlm.nih.gov/37741434/

4. Yuan, Zhen, Ding, Binbin. 2024. Coronavirus hijacks STX18-ATG14 axis-regulated lipophagy to evade an anti-viral effect. In Autophagy, 20, 1895-1896. doi:10.1080/15548627.2024.2330039. https://pubmed.ncbi.nlm.nih.gov/38477940/