Tomm70a-KO Mouse

TOMM70A, also known as translocase of outer mitochondrial membrane 70 homolog A, is a gene encoding an import component of the mitochondrial outer membrane. It is ubiquitously expressed in human tissues and plays a significant role in the import of nuclear-encoded mitochondrial proteins with internal targeting sites, like ADP/ATP carriers and uncoupling proteins [2]. The gene is involved in pathways related to mitochondrial biogenesis and function, which are crucial for normal cellular metabolism and energy production. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, could potentially be valuable in further elucidating its functions.

In bronchopulmonary dysplasia (BPD), TOMM70A, along with WIPI1, BAG3, and PRKCQ, was used to construct a diagnostic prediction model. BPD model mice had significantly lower expression levels of TOMM70A compared to controls, suggesting that these genes may influence BPD development by regulating immune responses and immune cells [1]. In triple-negative breast cancer, TOMM70A was identified as a candidate tumor suppressor gene. Down-regulation of its expression in four human TNBC cell lines led to increased cellular proliferation, and in tumor xenograft studies, it showed tumor suppressor activity [3]. In breast cancer patients, mitochondrial markers including TOMM70A were identified to predict recurrence, distant metastasis, and tamoxifen-resistance, with higher levels of TOMM70A associated with treatment failure [4]. In diffuse large B-cell lymphoma, TOMM70A was among 18 prognostic mitochondria-related genes used to construct a risk model, and differences in immune infiltration, expression of targeted-therapy-associated genes, and response to immunotherapy were observed between high-and low-risk groups based on this model [5].

In conclusion, TOMM70A is essential for mitochondrial protein import and thus for maintaining normal mitochondrial function. Model-based research, especially in disease-relevant models like BPD mouse models, triple-negative breast cancer cell lines and xenografts, and breast cancer patient cohorts, has revealed its potential roles in disease diagnosis, prognosis, and as a candidate tumor suppressor. These findings contribute to understanding the biological processes underlying these diseases and may offer new therapeutic strategies.

References:

1. Liu, Qingqing, Zhang, Meiyu, Xiang, Qingqing, He, Yi, Li, Fang. 2024. Development and validation of the prediction model based on autophagy-associated genes in bronchopulmonary dysplasia. In Annals of medicine, 56, 2433677. doi:10.1080/07853890.2024.2433677. https://pubmed.ncbi.nlm.nih.gov/39611552/

2. Edmonson, Angela M, Mayfield, Douglas K, Vervoort, Virginie, DuPont, Barbara R, Argyropoulos, George. . Characterization of a human import component of the mitochondrial outer membrane, TOMM70A. In Cell communication & adhesion, 9, 15-27. doi:. https://pubmed.ncbi.nlm.nih.gov/12200962/

3. Rangel, Roberto, Guzman-Rojas, Liliana, Kodama, Takahiro, Copeland, Neal G, Jenkins, Nancy A. 2017. Identification of New Tumor Suppressor Genes in Triple-Negative Breast Cancer. In Cancer research, 77, 4089-4101. doi:10.1158/0008-5472.CAN-17-0785. https://pubmed.ncbi.nlm.nih.gov/28724549/

4. Sotgia, Federica, Fiorillo, Marco, Lisanti, Michael P. 2017. Mitochondrial markers predict recurrence, metastasis and tamoxifen-resistance in breast cancer patients: Early detection of treatment failure with companion diagnostics. In Oncotarget, 8, 68730-68745. doi:10.18632/oncotarget.19612. https://pubmed.ncbi.nlm.nih.gov/28978152/

5. Zhou, Zhen-Zhong, Lu, Jia-Chen, Guo, Song-Bin, Zhou, Hui, Huang, Wei-Juan. . A Mitochondria-Related Signature in Diffuse Large B-Cell Lymphoma: Prognosis, Immune and Therapeutic Features. In Cancer medicine, 14, e70602. doi:10.1002/cam4.70602. https://pubmed.ncbi.nlm.nih.gov/39811936/