Immt, also known as inner membrane mitochondrial protein, is a key component of the mitochondrial contact site and cristae organizing system (MICOS), playing a vital role in maintaining inner mitochondrial membrane architecture and crista junction formation [2,3]. It is involved in processes related to mitochondrial quality control, such as mitophagy [1,4,5]. Given its significance in mitochondrial function, genetic models like gene knockout (KO) or conditional knockout (CKO) mouse models are valuable for studying its functions.

Genetic ablation of Immt in adult mice via tamoxifen-inducible ROSA-CreERT2-mediated deletion disrupted the MICOS complex, increased mitochondria size, altered cristae morphology, and was lethal within 12 days. These mice showed defective intestinal muscle function (paralytic ileus) leading to dehydration and bone marrow hypocellularity, demonstrating the importance of Immt in vivo in both hematopoietic and non-hematopoietic tissues [2].

In conclusion, Immt is essential for maintaining mitochondrial structure and function through its role in the MICOS complex. The Immt KO/CKO mouse models have revealed its significance in physiological processes, with implications for understanding diseases where mitochondrial function is compromised, such as in the observed lethal phenotypes related to disrupted mitochondrial function in these mouse models [2].

References:

1. Zhang, Ting, Liu, Qian, Gao, Weihua, Sehgal, Sheikh Arslan, Wu, Hao. 2021. The multifaceted regulation of mitophagy by endogenous metabolites. In Autophagy, 18, 1216-1239. doi:10.1080/15548627.2021.1975914. https://pubmed.ncbi.nlm.nih.gov/34583624/

2. Rockfield, Stephanie M, Turnis, Meghan E, Rodriguez-Enriquez, Ricardo, Vogel, Peter, Opferman, Joseph T. 2024. Genetic ablation of Immt induces a lethal disruption of the MICOS complex. In Life science alliance, 7, . doi:10.26508/lsa.202302329. https://pubmed.ncbi.nlm.nih.gov/38467404/

3. Lin, Hung-Yu, Wu, Hsing-Ju, Chu, Pei-Yi. 2023. Multi-omics and experimental analysis unveil theragnostic value and immunological roles of inner membrane mitochondrial protein (IMMT) in breast cancer. In Journal of translational medicine, 21, 189. doi:10.1186/s12967-023-04035-4. https://pubmed.ncbi.nlm.nih.gov/36899366/

4. Nan, Dongqi, Rao, Chenglong, Tang, Zhiheng, Zou, Quanming, Li, Qian. 2024. Burkholderia pseudomallei BipD modulates host mitophagy to evade killing. In Nature communications, 15, 4740. doi:10.1038/s41467-024-48824-x. https://pubmed.ncbi.nlm.nih.gov/38834545/

5. Nan, Dongqi, Mao, Xuhu, Li, Qian. 2024. Burkholderia pseudomallei BipD initiates mitophagy to evade killing by hijacking host KLHL9-KLHL13-CUL3 E3 ligase to ubiquitinate IMMT. In Autophagy, 20, 2830-2832. doi:10.1080/15548627.2024.2403125. https://pubmed.ncbi.nlm.nih.gov/39265641/