Cmc1, a mitochondrial electron transport chain (ETC) complex IV chaperon protein, is crucial for the biogenesis of cytochrome c oxidase [2,4]. It functions in the mitochondrial intermembrane space and is involved in the early assembly of complex IV [2]. Its role has significant implications for mitochondrial respiration and overall cellular energy metabolism, and genetic models such as knockout mice have been used to explore its functions [1].

In T cell immunity, Cmc1 gene knockout mice studies revealed that Cmc1 is a positive regulator in CD8+ T cells activation and terminal differentiation. Genetic loss of Cmc1 inhibits the development of CD8+ T cell exhaustion in mice, and instead, deletion prompts T cells to differentiate into metabolically and functionally quiescent cells with increased memory-like features [1]. In colon adenocarcinoma, Cmc1 expression was found to be low in tissues, and functional experiments suggest it may control the proliferation ability of CRC cells [3].

In conclusion, Cmc1 plays essential roles in mitochondrial complex IV biogenesis and T cell-related immune responses. The use of Cmc1 gene knockout mouse models has provided insights into its functions in T cell-based immunotherapies and potential applications in treating colon adenocarcinoma, highlighting its significance in both basic biological processes and disease-related research [1,3].

References:

1. Chen, Yuwen, Gao, Jie, Ma, Mingyue, Cheng, Zhouli, Wu, Duojiao. 2024. The potential role of CMC1 as an immunometabolic checkpoint in T cell immunity. In Oncoimmunology, 13, 2344905. doi:10.1080/2162402X.2024.2344905. https://pubmed.ncbi.nlm.nih.gov/38659649/

2. Bourens, Myriam, Barrientos, Antoni. 2017. A CMC1-knockout reveals translation-independent control of human mitochondrial complex IV biogenesis. In EMBO reports, 18, 477-494. doi:10.15252/embr.201643103. https://pubmed.ncbi.nlm.nih.gov/28082314/

3. Xu, Zipeng, Gong, Jiantao, Hu, Weidong, Yuan, Yihang, Chen, Chaobo. 2024. The Risk Genes S1PR5, CMC1, and ASAH1 as Potential Targets for the Diagnosis, Immunotherapy, and Treatment of Colon Adenocarcinoma by Single-Cell and Bulk RNA Sequencing Analysis. In Current medicinal chemistry, , . doi:10.2174/0109298673331144241009082052. https://pubmed.ncbi.nlm.nih.gov/39513308/

4. Horn, Darryl, Zhou, Wen, Trevisson, Eva, Salviati, Leonardo, Barrientos, Antoni. 2010. The conserved mitochondrial twin Cx9C protein Cmc2 Is a Cmc1 homologue essential for cytochrome c oxidase biogenesis. In The Journal of biological chemistry, 285, 15088-15099. doi:10.1074/jbc.M110.104786. https://pubmed.ncbi.nlm.nih.gov/20220131/