Ppm1k, also named as PP2Cm or branched-chain α-ketoacid dehydrogenase complex phosphatase, is a member of the metal-dependent phosphatase family. It is predominantly located in the mitochondrial matrix and plays a crucial role in the metabolism of branched-chain amino acids (BCAAs) [3,4]. It is also involved in various cellular functions and development across different tissues [4]. Genetic models, like knockout mouse models, are valuable for studying its functions [1].

In Ppm1k-deficient female mice, BCAA levels increased, and they exhibited PCOS-like traits such as hyperandrogenemia and abnormal follicle development [1]. This shows that Ppm1k deficiency-impaired BCAA catabolism can cause the occurrence and development of PCOS [1]. Also, knockdown of PPM1K in neurons led to defective BCAA catabolism, which induced neuronal ferroptosis after cerebral ischemia-reperfusion injury [2].

In conclusion, Ppm1k is essential for the regulation of BCAA metabolism. Model-based research, especially using Ppm1k KO mouse models, has revealed its role in diseases like PCOS and cerebral ischemia-reperfusion injury, highlighting its importance in understanding the mechanisms of these diseases and potentially guiding therapeutic strategies [1,2].

References:

1. Mu, Liangshan, Ye, Zhenhong, Hu, Junhao, Zhao, Yue, Qiao, Jie. 2023. PPM1K-regulated impaired catabolism of branched-chain amino acids orchestrates polycystic ovary syndrome. In EBioMedicine, 89, 104492. doi:10.1016/j.ebiom.2023.104492. https://pubmed.ncbi.nlm.nih.gov/36863088/

2. Li, Tao, Zhao, Lili, Li, Ye, Kuang, Fang, Zhang, Guilian. 2023. PPM1K mediates metabolic disorder of branched-chain amino acid and regulates cerebral ischemia-reperfusion injury by activating ferroptosis in neurons. In Cell death & disease, 14, 634. doi:10.1038/s41419-023-06135-x. https://pubmed.ncbi.nlm.nih.gov/37752100/

3. Kamada, Rui, Kudoh, Fuki, Ito, Shogo, Omichinski, James G, Sakaguchi, Kazuyasu. 2020. Metal-dependent Ser/Thr protein phosphatase PPM family: Evolution, structures, diseases and inhibitors. In Pharmacology & therapeutics, 215, 107622. doi:10.1016/j.pharmthera.2020.107622. https://pubmed.ncbi.nlm.nih.gov/32650009/

4. Mao, Yuanling, Feng, Jing. 2024. Phosphatase activity-based PPM1K: a key player in the regulation of mitochondrial function and its multifaceted impact in diseases. In Molecular and cellular biochemistry, 480, 2815-2826. doi:10.1007/s11010-024-05188-6. https://pubmed.ncbi.nlm.nih.gov/39695034/