Atg5, short for autophagy related 5, is a key component in autophagy. It is essential for the formation of autophagosomes, a hallmark of autophagy. Atg5 binds with Atg12 and Atg16L1 to form an E3 like ligase complex necessary for autophagosome expansion. Autophagy, in which Atg5 is involved, plays a central role in maintaining cellular homeostasis, nutrient and energy recycling, and is associated with various biological processes and diseases [2]. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, are valuable for studying Atg5.

In Atg5flox/flox; Stra8-iCre mutant mice (a CKO model), testicular autophagy activity decreased, leading to reduced male fertility, abnormal sperm development, and sperm individualization issues [3]. In proximal tubule-specific autophagy-deficient mice (KO model for epithelial Atg5), ablation of Atg5 genes impaired autophagy, enhanced NF-κB activation, macrophage and lymphocyte infiltration, and proinflammatory cytokines production in obstructed kidneys [1]. Myeloid cell-specific Atg5 knockout (MΦ atg5 -/-) mice had reduced renal fibrosis and macrophage recruitment after ischemia/reperfusion and unilateral ureteral obstruction injury, as Atg5 deficiency impaired the CCL20-CCR6 axis [4].

In conclusion, model-based research, especially KO/CKO mouse models, has revealed that Atg5 is crucial for autophagy-related functions. It impacts male fertility, renal inflammation, and fibrosis. These findings contribute to understanding the role of Atg5 in specific disease areas such as male infertility and kidney-related diseases.

References:

1. Peng, Xuan, Wang, Yating, Li, Huiyan, Zhou, Yi, Mao, Haiping. 2019. ATG5-mediated autophagy suppresses NF-κB signaling to limit epithelial inflammatory response to kidney injury. In Cell death & disease, 10, 253. doi:10.1038/s41419-019-1483-7. https://pubmed.ncbi.nlm.nih.gov/30874544/

2. Changotra, Harish, Kaur, Sargeet, Yadav, Suresh Singh, Parkash, Jyoti, Duseja, Ajay. 2022. ATG5: A central autophagy regulator implicated in various human diseases. In Cell biochemistry and function, 40, 650-667. doi:10.1002/cbf.3740. https://pubmed.ncbi.nlm.nih.gov/36062813/

3. Huang, Qian, Liu, Yunhao, Zhang, Shiyang, Hess, Rex A, Zhang, Zhibing. 2020. Autophagy core protein ATG5 is required for elongating spermatid development, sperm individualization and normal fertility in male mice. In Autophagy, 17, 1753-1767. doi:10.1080/15548627.2020.1783822. https://pubmed.ncbi.nlm.nih.gov/32677505/

4. Zhu, Yufeng, Tan, Jiexing, Wang, Yuanzhan, Zhu, Wei, Gong, Li. 2024. Atg5 deficiency in macrophages protects against kidney fibrosis via the CCR6-CCL20 axis. In Cell communication and signaling : CCS, 22, 223. doi:10.1186/s12964-024-01600-2. https://pubmed.ncbi.nlm.nih.gov/38594728/