Me1, also known as malic enzyme 1, is a cytosolic protein that catalyzes the conversion of malate to pyruvate, generating NADPH from NADP in the process [1]. It is involved in lipid and cholesterol biosynthesis, participates in glycolysis-tricarboxylic acid cycle connection, and is crucial for maintaining redox homeostasis and lipogenesis [1,2]. Early research identified it as an insulin-regulated gene in liver and adipose tissues and a transcriptional target of thyroxine [1].

Global and endothelial-specific Me1 knockout mice were used to study its role in pulmonary hypertension (PH) [2]. The results showed that ME1 protein level and enzymatic activity were highly elevated in lung tissues of patients and mice with PH, mainly in vascular endothelial cells. Global knockout of Me1 protected mice from developing hypoxia-or SU5416/hypoxia-induced PH, and endothelial-specific Me1 deletion similarly attenuated pulmonary vascular remodeling and PH development, suggesting a critical role of endothelial Me1 in PH [2]. In addition, in cancer research, knockdown of Me1 in cancer cells increased intracellular ROS levels, impaired lipogenesis, retarded proliferation, and increased anoikis, while sparing normal cells [3].

In conclusion, Me1 plays essential roles in metabolism-related biological processes, especially in lipid metabolism, redox homeostasis, and lipogenesis. Gene knockout mouse models have revealed its significant contribution to diseases such as pulmonary hypertension and cancer, highlighting its potential as a therapeutic target in these disease areas.