Atg3, short for Autophagy-related gene 3, is a key gene in the autophagy pathway. It acts as an E2 ubiquitin-like conjugating enzyme in the ATG8 conjugation system, crucial for phagophore elongation during autophagy, an evolutionarily conserved catabolic process maintaining cellular, tissue, and organismal homeostasis [2].

Genetic knockdown of Atg3 in mice and human hepatocytes ameliorates p63-and diet-induced steatosis, while its overexpression increases the lipid load in hepatocytes. Inhibition of hepatic Atg3 improves fatty acid metabolism by reducing c-Jun N-terminal protein kinase 1 (JNK1), increasing sirtuin 1 (SIRT1), carnitine palmitoyltransferase 1a (CPT1a), and mitochondrial function, indicating its role in non-alcoholic fatty liver disease (NAFLD) [1].

In conclusion, Atg3 is essential for autophagosome formation through its role in the ATG8 conjugation system. The study of Atg3 knockout mouse models has revealed its contribution to the progression of NAFLD, highlighting its importance in lipid metabolism-related diseases. This research provides insights into potential therapeutic targets for treating NAFLD [1].

References:

1. da Silva Lima, Natália, Fondevila, Marcos F, Nóvoa, Eva, Aspichueta, Patricia, Nogueiras, Ruben. 2021. Inhibition of ATG3 ameliorates liver steatosis by increasing mitochondrial function. In Journal of hepatology, 76, 11-24. doi:10.1016/j.jhep.2021.09.008. https://pubmed.ncbi.nlm.nih.gov/34555423/

2. Fang, Dongmei, Xie, Huazhong, Hu, Tao, Shan, Hao, Li, Min. 2021. Binding Features and Functions of ATG3. In Frontiers in cell and developmental biology, 9, 685625. doi:10.3389/fcell.2021.685625. https://pubmed.ncbi.nlm.nih.gov/34235149/