Mdh1-flox Mouse

Mdh1, short for malate dehydrogenase 1, is a key enzyme involved in the malate-aspartate shuttle and the tricarboxylic acid cycle [6]. It catalyzes the reversible oxidation of L-malate to oxaloacetate, playing essential roles in mitochondrial NADH supply for oxidative phosphorylation and thus is of great biological importance in energy metabolism [6].

In acute liver failure (ALF), deacetylation of Mdh1 at K118 promotes neutrophil extracellular trap (NET) formation, a novel mode of cell death, which in turn aggravates the progression of ALF [1,3,4]. In ALI, the citrate cycle pathway including Mdh1 is inactivated, and Mdh1 promotes the cell vitality of primary alveolar epithelial type II (AT2) cells by increasing glucose intake [2]. In pancreatic ductal adenocarcinoma (PDAC), Mdh1 is required for maintaining the levels of the autophagy initiator ULK1 during autophagosome formation [5]. In addition, MDH1 deficiency in humans is associated with early-onset severe encephalopathy [6].

In conclusion, Mdh1 is crucial in multiple biological processes such as energy metabolism, cell viability regulation, autophagy, and NET formation. Studies, especially those using relevant disease models like ALF, ALI, and PDAC, have revealed its important roles in these disease conditions. The understanding of Mdh1's functions in these models provides insights into the pathogenesis of related diseases, which may help develop new therapeutic strategies.