Prkaa1, also known as AMPKα1, is the α -subunit of 5 -AMP -activated protein kinase. This kinase is a major cellular sensor of energy and nutrients, playing a key role in regulating cellular energy metabolism through phosphorylation [1,2,7]. It is involved in multiple biological processes and associated with various pathways, such as autophagy, redox balance, and mitophagy, which are crucial for cell survival, development, and homeostasis [5,6,9].

In gene-knockout (KO) mouse models, endothelial-specific Prkaa1 knockout in HFD-fed mice alleviated HFD-induced metabolic syndromes, including decreased body weight, enhanced glucose clearance, and relieved adipose inflammation and hepatic steatosis. Mechanistically, PRKAA1 knockdown in cultured endothelial cells reduced glycolysis, fatty acid oxidation, and suppressed transcription of inflammatory molecules [2]. In Prkaa1-deficient mice, autophagy-dependent mitochondrial clearance during erythrocyte maturation was defective, leading to enhanced oxidative stress, shortened erythrocyte lifespan, and anemia [9].

In conclusion, Prkaa1 is essential for regulating cellular energy metabolism, autophagy, and redox balance. The Prkaa1 KO mouse models have revealed its significant role in metabolic syndrome and erythrocyte maturation. Additionally, studies on Prkaa1 genetic polymorphisms have shown its association with the risk of gastric and esophageal cancers, indicating its importance in cancer-related research [1,3,4,8].

References:

1. Chen, Yongyi, Chen, Siyu, Zhu, Jing, Yu, Qiong, Xu, Songxiao. 2023. PRKAA1 predicts prognosis and is associated with immune characteristics in gastric cancer. In Functional & integrative genomics, 23, 252. doi:10.1007/s10142-023-01176-z. https://pubmed.ncbi.nlm.nih.gov/37482545/

2. Yang, Qiuhua, Ma, Qian, Xu, Jiean, Belin de Chantemèle, Eric J, Huo, Yuqing. 2021. Endothelial AMPKα1/PRKAA1 exacerbates inflammation in HFD-fed mice. In British journal of pharmacology, 179, 1661-1678. doi:10.1111/bph.15742. https://pubmed.ncbi.nlm.nih.gov/34796475/

3. Jiang, You, Li, Wenbo, Lu, Jun, Zhao, Xin, Li, Liang. . Association between PRKAA1 rs13361707 T>C polymorphism and gastric cancer risk: Evidence based on a meta-analysis. In Medicine, 97, e0302. doi:10.1097/MD.0000000000010302. https://pubmed.ncbi.nlm.nih.gov/29620653/

4. Yu, Shuyong, Tu, Ruisha, Chen, Zhaowei, Zhang, Ronglin, Li, Yini. 2023. Association of PTGER4 and PRKAA1 genetic polymorphisms with gastric cancer. In BMC medical genomics, 16, 209. doi:10.1186/s12920-023-01645-1. https://pubmed.ncbi.nlm.nih.gov/37670284/

5. Zhang, Yangmei, Zhou, Xichang, Cheng, Xue, Chen, Kai, Li, Yang. 2022. PRKAA1, stabilized by FTO in an m6A-YTHDF2-dependent manner, promotes cell proliferation and glycolysis of gastric cancer by regulating the redox balance. In Neoplasma, 69, 1338-1348. doi:10.4149/neo_2022_220714N714. https://pubmed.ncbi.nlm.nih.gov/36305690/

6. Tang, Yanling, Zhang, Jingjing, Hu, Zeyu, Xing, Hengrui, Niu, Qiang. 2023. PRKAA1 induces aberrant mitophagy in a PINK1/Parkin-dependent manner, contributing to fluoride-induced developmental neurotoxicity. In Ecotoxicology and environmental safety, 255, 114772. doi:10.1016/j.ecoenv.2023.114772. https://pubmed.ncbi.nlm.nih.gov/36924562/

7. Zhang, Yangmei, Zhou, Xichang, Cheng, Long, Zhang, Youwei, Sun, Sanyuan. 2019. PRKAA1 Promotes Proliferation and Inhibits Apoptosis of Gastric Cancer Cells Through Activating JNK1 and Akt Pathways. In Oncology research, 28, 213-223. doi:10.3727/096504019X15668125347026. https://pubmed.ncbi.nlm.nih.gov/31558185/

8. Li, Cheng-Lin, Zhao, Jian-Qiang, Zang, Bao. 2020. PRKAA1 rs13361707 C/T polymorphism confers decreased susceptibility to esophageal cancer: A case-control study. In Journal of clinical laboratory analysis, 34, e23406. doi:10.1002/jcla.23406. https://pubmed.ncbi.nlm.nih.gov/32488984/

9. Zhu, Huaiping, Foretz, Marc, Xie, Zhonglin, Viollet, Benoit, Zou, Ming-Hui. 2014. PRKAA1/AMPKα1 is required for autophagy-dependent mitochondrial clearance during erythrocyte maturation. In Autophagy, 10, 1522-34. doi:10.4161/auto.29197. https://pubmed.ncbi.nlm.nih.gov/24988326/