MTCH2, or 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, being required for the insertion of diverse transmembrane proteins [1]. MTCH2 is also involved in multiple biological processes, such as mitochondrial apoptosis, metabolic shift, mitochondrial fusion/fission, which are crucial for overall cellular function and organismal homeostasis [2].

In various disease-related studies, adipose-specific MTCH2 depletion in mice protects against high-fat-diet-induced obesity and metabolic disorders, suggesting it negatively regulates energy homeostasis by suppressing thermogenesis via a Bcl-2-dependent autophagy-regulation mechanism [3]. In breast cancer cells, over-expression of MTCH2 promotes cellular proliferation and cycle progression via the PI3K/Akt pathway, while its silencing has the opposite effect [4]. In osteosarcoma, APOC1 promotes the cancer's progression by binding to MTCH2 [5]. Also, knockdown of MTCH2 in Drosophila heart tubes leads to a dilated and poorly functioning heart tube, reduced adiposity, and shortened lifespan, with impaired oxygen consumption in the presence of glucose [6]. In lipid homeostasis research, MTCH2 knockdown reduced lipid accumulation in adipocyte-like cells, C. elegans, and mice, while over-expression increased fat accumulation [7].

In conclusion, MTCH2 is essential for mitochondrial outer membrane protein insertion and plays a significant role in multiple biological processes. Model-based research, especially gene-knockout studies in mice and Drosophila, has revealed its crucial functions in metabolic diseases, cancers, and heart-related conditions, providing potential therapeutic targets for these diseases.