Atg13-KO Mouse

Atg13, a key component in the autophagy process, is part of the Atg1 kinase complex in yeast and the orthologous ULK1 kinase complex in vertebrates. It functions in initiating autophagy, sensing nutritional status signals, recruiting downstream ATG proteins to the autophagosome formation site, and governing autophagosome formation. Autophagy is an intracellular degradation process involved in recycling cytoplasmic components and removing various cellular elements [2,3].

In PM2.5-induced pulmonary fibrosis, PM2.5-downregulated ALKBH5 promotes m6A modification of Atg13 mRNA at site 767 in lung epithelial cells. Atg13-mediated ULK complex positively regulates autophagy and inflammation in these cells. Knockout of ALKBH5 in mice further accelerates ULK complex-regulated autophagy, inflammation, and pulmonary fibrosis, highlighting the role of site-specific m6A methylation on Atg13 mRNA in autophagy-dependent pulmonary fibrosis [1]. Atg13-deficient mice die in utero, showing growth retardation and myocardial growth defects. In cultured fibroblasts, Atg13 deficiency blocks autophagosome formation at an upstream step, and deletion of Atg13 enhances sensitivity to TNF-α-induced apoptosis [4].

In conclusion, Atg13 is essential for autophagy, with its deficiency having significant impacts on cardiac development and apoptosis sensitivity. In the context of PM2.5-induced pulmonary fibrosis, its mRNA methylation is crucial in autophagy-related disease progression. Studies using Atg13-deficient mouse models have provided valuable insights into its role in these biological processes and disease conditions.

References:

1. Ning, Jie, Pei, Zijie, Wang, Mengruo, Leng, Shuguang, Zhang, Rong. 2023. Site-specific Atg13 methylation-mediated autophagy regulates epithelial inflammation in PM2.5-induced pulmonary fibrosis. In Journal of hazardous materials, 457, 131791. doi:10.1016/j.jhazmat.2023.131791. https://pubmed.ncbi.nlm.nih.gov/37295326/

2. Alers, Sebastian, Wesselborg, Sebastian, Stork, Björn. . ATG13: just a companion, or an executor of the autophagic program? In Autophagy, 10, 944-56. doi:10.4161/auto.28987. https://pubmed.ncbi.nlm.nih.gov/24879146/

3. Wang, Qiuling, Hou, Suiwen. 2022. The emerging roles of ATG1/ATG13 kinase complex in plants. In Journal of plant physiology, 271, 153653. doi:10.1016/j.jplph.2022.153653. https://pubmed.ncbi.nlm.nih.gov/35255243/

4. Kaizuka, Takeshi, Mizushima, Noboru. 2015. Atg13 Is Essential for Autophagy and Cardiac Development in Mice. In Molecular and cellular biology, 36, 585-95. doi:10.1128/MCB.01005-15. https://pubmed.ncbi.nlm.nih.gov/26644405/