Mcu, short for mitochondrial calcium uniporter, is a key regulator for mitochondrial and cellular homeostasis. It forms a complex in the inner mitochondrial membrane for Ca2+ uptake, regulating oxidative metabolism, cell death, and energy metabolism [4]. Mitochondrial Ca2+ homeostasis, controlled by Mcu, is involved in various biological processes, and genetic models are valuable for studying its functions.

In global Mcu knockout mice, isoproterenol (ISO)-induced cardiac hypertrophy, fibrosis, contractile dysfunction, and cardiomyocyte death were exacerbated, indicating Mcu upregulation as a compensatory mechanism against stress-induced pathological cardiac remodeling [1]. Heterozygous Mcu knockout mice showed improved liver function, ameliorated pathological damage, less mitochondrial fragmentation, and mitophagy after cadmium exposure, suggesting Mcu's role in cadmium-induced hepatotoxicity [2]. Mice with a deleted Mcu gene in muscle, lacking acute mitochondrial Ca2+ uptake, had greater fatty acid oxidation (FAO) and less adiposity, highlighting Mcu's role in regulating metabolism [3]. Inhibition of Mcu in an intestinal ischemia-reperfusion (IIR) model using C57BL/6 mice alleviated IIR injury, mitochondrial dysfunction, and apoptosis by reducing Drp1-dependent mitochondrial fission [5].

In conclusion, Mcu is crucial for maintaining mitochondrial and cellular homeostasis, participating in processes like metabolism, cell death, and stress-related responses. Gene knockout mouse models have revealed its significance in cardiac, liver, muscle-related metabolic, and intestinal ischemia-reperfusion diseases, providing insights into disease mechanisms and potential therapeutic targets.