MTCH2, short for mitochondrial carrier homolog 2, is a member of the solute carrier 25 family located on the outer mitochondrial membrane. It functions as a mitochondrial outer membrane protein insertase, facilitating the insertion of various types of proteins into the membrane [1]. MTCH2 is also involved in multiple pathways such as mitochondrial apoptosis, fusion/fission, metabolic shift between glycolysis and oxidative phosphorylation, and epithelial-mesenchymal transition, playing a crucial role in biological processes like embryonic development, reproduction, and maintaining lipid and energy homeostasis [2,3,5]. Genetic models, including KO/CKO mouse models, have been valuable for studying its functions.

In mice, adipose-specific MTCH2 depletion protects against high-fat-diet-induced obesity and metabolic disorders. MTCH2 deficiency promotes energy expenditure by stimulating thermogenesis in brown adipose tissue and browning of subcutaneous white adipose tissue, revealing its role as a negative regulator of energy homeostasis [3]. Knocking down Mtch in Drosophila heart tubes leads to a dilated and poorly functioning heart tube, reduced adiposity, and shortened lifespan, indicating its importance in heart function and metabolism [4]. In addition, MTCH2 knockdown reduces lipid accumulation in adipocyte-like cells in vitro and in C. elegans and mice in vivo, while its overexpression increases fat accumulation, highlighting its role in lipid homeostasis [5].

In conclusion, MTCH2 is essential for multiple biological functions, especially in regulating mitochondrial function, energy and lipid homeostasis. Studies using KO/CKO mouse models and other genetic models have significantly enhanced our understanding of its roles in obesity, heart failure, and other related diseases, providing potential therapeutic targets for these conditions.