Mdh2-flox Mouse

Mdh2, or malate dehydrogenase 2, is a key enzyme in the tricarboxylic acid (TCA) cycle. The TCA cycle is crucial for cellular energy production through oxidative phosphorylation and also contributes to anabolic processes. Mdh2 has significant biological importance in maintaining normal cellular metabolism and is involved in multiple physiological and pathological processes [1,2,3,4,5,6,8].

MDH2 silencing in ovarian cancer cells represses mitochondrial respiration and cell proliferation both in vitro and in vivo, indicating its role in promoting ovarian cancer malignancy [1]. In clear cell renal cell carcinoma (ccRCC), knocking out MDH2 enhances the proliferation of ccRCC cells, and MDH2 inhibits ccRCC proliferation by promoting ferroptosis [4]. In hepatocellular carcinoma (HCC), MDH2 deficiency inhibits HCC cell growth and enhances their sensitivity to ferroptosis, and MDH2 resists ferroptosis by stabilizing GPX4 [5]. In ischemic stroke, microglial lnc-U90926 binds to MDH2, affecting the decay of CXCL2 mRNA and thus neutrophil infiltration [7].

In conclusion, Mdh2 is essential for maintaining mitochondrial respiration and normal cell metabolism. Its dysregulation is closely associated with the development of various cancers such as ovarian, ccRCC, and HCC, as well as ischemic stroke. Gene knockout and knockdown models have been crucial in revealing Mdh2's role in these disease conditions, providing potential therapeutic targets for treatment [1,4,5,7].