Mpst, or 3-mercaptopyruvate sulfurtransferase, is a mitochondrial cysteine-catabolizing enzyme. It is involved in hydrogen sulfide (H₂S) biosynthesis, protein S-persulfidation, and tRNA thiolation [4,5]. It plays a role in multiple biological pathways such as mitochondrial protein import, bioenergetics, and apoptosis regulation, which are crucial for maintaining normal physiological functions [2,5]. Genetic models, like gene knockout (KO) mouse models, have been instrumental in studying its functions.

In KO mouse models, Mpst deficiency significantly aggravated murine colitis symptoms, exacerbated inflammatory responses and apoptosis, and inhibited epithelium stem cell-derived organoid formation, likely through regulating the AKT/apoptosis axis in intestinal epithelial cells (IECs) [1]. In obese mice, Mpst deletion led to fat accumulation through transcriptional and metabolic maladaptation, with activated HIF1α, downregulated TIM/TOM complex subunits, and impaired mitochondrial protein import [2]. Also, in Cth/Mpst double-knockout mice, there was enhanced vasorelaxation and reduced blood pressure via upregulation of the eNOS/sGC pathway [3].

In conclusion, Mpst is essential for maintaining normal physiological functions, especially in intestinal protection, metabolism, and cardiovascular homeostasis. Studies using Mpst KO mouse models have revealed its significant roles in inflammatory bowel disease, obesity, and blood pressure regulation, providing potential therapeutic targets for these diseases.