Me1-flox Mouse

Me1, or malic enzyme 1, is a cytosolic protein that catalyzes the conversion of malate to pyruvate, generating NADPH from NADP in the process. It is involved in key metabolic pathways such as lipid and cholesterol biosynthesis, and is a transcriptional target of thyroxine [2]. ME1 has been linked to multiple biological processes and diseases, especially cancer [2].

Global and endothelial-specific ME1 knockout mice have been used to study its role in various conditions. In pulmonary hypertension (PH), global knockout of ME1 protected mice from developing hypoxia-or SU5416/hypoxia-induced PH, and endothelial-specific ME1 deletion attenuated pulmonary vascular remodeling and PH development. Mechanistically, ME1 inhibition promoted downstream adenosine production and activated A2AR-mediated adenosine signaling in endothelial cells [4]. In colorectal cancer, ME1 promotes lipid metabolism, NADPH production, and tumorigenesis. Its phosphorylation and acetylation states are dynamically regulated by enzymes like PGAM5, NEK1, ACAT1, and SIRT6, influencing NADPH generation and the susceptibility to colorectal tumorigenesis [1]. In gastric cancer, knockdown of ME1 depleted NADPH, induced ROS, and led to cell apoptosis under oxidative stress conditions, while promoting tumor growth, lung metastasis, and peritoneal dissemination in vivo [3].

In conclusion, Me1 is crucial for metabolic processes, especially those related to NADPH production. Gene knockout mouse models have revealed its significant role in diseases such as pulmonary hypertension and various cancers, highlighting its potential as a therapeutic target in these disease areas.