Mdh1-KO Mouse

Mdh1, short for malate dehydrogenase 1, is a key enzyme involved in the citrate cycle pathway [2]. It catalyzes the interconversion between malate and oxaloacetate, playing a crucial role in energy metabolism processes. This function is vital for various biological processes such as cell viability maintenance and metabolite regulation. Genetic models, like KO or CKO mouse models, can be valuable in further exploring its functions.

In acute liver failure (ALF), deacetylation of MDH1 at K118 promotes NETosis, a novel mode of cell death, and aggravates PANoptosis through endoplasmic reticulum stress signaling, thus accelerating the progression of ALF [1,3]. In acute lung injury (ALI), inactivation of MDH1 in the citrate cycle pathway affects the glycolysis of primary alveolar epithelial type II (AT2) cells. Restoring MDH1 function promotes AT2 cell vitality by increasing glucose intake, suggesting its potential as a therapeutic target for ALI [2]. In pancreatic ductal adenocarcinoma (PDAC), MDH1 is required for maintaining the levels of the essential autophagy initiator serine-threonine kinase ULK1 during autophagosome formation, regulating autophagy in PDAC cells [4].

In conclusion, MDH1 is essential for energy metabolism-related biological processes. Studies using model-based research, especially in relation to diseases like ALF, ALI, and PDAC, have revealed its role in cell death regulation, cell viability, and autophagy. These findings contribute to understanding the pathogenesis of these diseases and potentially developing new treatment strategies.

References:

1. Wang, Yukun, Shi, Chunxia, Guo, Jin, Zhang, Long, Gong, Zuojiong. 2024. IDH1/MDH1 deacetylation promotes acute liver failure by regulating NETosis. In Cellular & molecular biology letters, 29, 8. doi:10.1186/s11658-023-00529-7. https://pubmed.ncbi.nlm.nih.gov/38172700/

2. Hu, Mu, Yang, JieLai, Xu, Yang, Liu, Jiao. 2022. MDH1 and MDH2 Promote Cell Viability of Primary AT2 Cells by Increasing Glucose Uptake. In Computational and mathematical methods in medicine, 2022, 2023500. doi:10.1155/2022/2023500. https://pubmed.ncbi.nlm.nih.gov/36158123/

3. Shi, Chunxia, Wang, Yukun, Guo, Jin, Zhang, Yanqiong, Gong, Zuojiong. 2024. Deacetylated MDH1 and IDH1 aggravates PANoptosis in acute liver failure through endoplasmic reticulum stress signaling. In Cell death discovery, 10, 275. doi:10.1038/s41420-024-02054-8. https://pubmed.ncbi.nlm.nih.gov/38851781/

4. New, Maria, Van Acker, Tim, Sakamaki, Jun-Ichi, Howell, Michael, Tooze, Sharon A. 2019. MDH1 and MPP7 Regulate Autophagy in Pancreatic Ductal Adenocarcinoma. In Cancer research, 79, 1884-1898. doi:10.1158/0008-5472.CAN-18-2553. https://pubmed.ncbi.nlm.nih.gov/30765601/