TOMM34, the 34-kDa translocase of the outer mitochondrial membrane, is a co-chaperone of Hsp70 and Hsp90. It is part of the cytosolic complex involved in mitochondrial protein import. It has been associated with pathways like oxidative phosphorylation, citric acid cycle, and purine and amino acid metabolism, as well as NOTCH -, MAPK -, and STAT3-signaling [8].

TOMM34 has been found to be highly expressed in many cancers such as colon [1], oral squamous cell carcinoma (OSCC) [2,6], epithelial ovarian cancer [4], urothelial carcinoma of the bladder [5], and early invasive breast cancer [9]. In colon cancer, its high expression correlates with immune cell infiltration and worse prognosis [1]. In OSCC, it promotes cell proliferation, migration, invasion, and modulates mitochondrial function [2]. In COVID-19 and influenza, viral induction of TOMM34 is positively correlated with hyperinflammation, as it recruits TRAF6 to facilitate NF-κB activation [3]. In hepatocellular carcinoma, it is upregulated in response to metformin-induced metabolic stress, interacting with ATP5B to preserve F1FO-ATPase activity and promote tumor metastasis [7].

In conclusion, TOMM34 plays crucial roles in maintaining mitochondrial function, cell proliferation, and immune-related processes. Its overexpression in various cancers and association with poor prognosis highlight its potential as a biomarker and therapeutic target. In severe viral infections, its role in hyperinflammation also makes it an important target for immune intervention strategies.

References:

1. Li, Zhigui, Yang, Hongzhao, Liu, Jianbo, Li, Li, Wang, Xiaodong. 2023. TOMM34 serves as a candidate therapeutic target associated with immune cell infiltration in colon cancer. In Frontiers in oncology, 13, 947364. doi:10.3389/fonc.2023.947364. https://pubmed.ncbi.nlm.nih.gov/36845719/

2. Huang, Yunyi, Chen, Zhipei, Chen, Xuanyi, Chen, Xiaohua, Xu, Meng. 2022. TOMM34 promotes cell proliferation, migration, and invasion of OSCC and modulates mitochondrial function. In Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, 52, 47-55. doi:10.1111/jop.13382. https://pubmed.ncbi.nlm.nih.gov/36367442/

3. Shi, Qiwen, Zhang, Pengfei, Hu, Qingtao, Zhu, Wenting, Qi, Nan. 2024. Role of TOMM34 on NF-κB activation-related hyperinflammation in severely ill patients with COVID-19 and influenza. In EBioMedicine, 108, 105343. doi:10.1016/j.ebiom.2024.105343. https://pubmed.ncbi.nlm.nih.gov/39276680/

4. Muller, Petr, Coates, Philip J, Nenutil, Rudolf, Brychtova, Veronika, Vojtesek, Borivoj. 2019. Tomm34 is commonly expressed in epithelial ovarian cancer and associates with tumour type and high FIGO stage. In Journal of ovarian research, 12, 30. doi:10.1186/s13048-019-0498-0. https://pubmed.ncbi.nlm.nih.gov/30917858/

5. Ahmed, Mohamed A H, Ali, Mohamed Hassan, Abbas, Hashem Hafez, Elatrash, Gamal Ali, Foda, Abd AlRahman Mohammad. 2018. Expression of TOMM34 and Its Clinicopathological Correlations in Urothelial Carcinoma of the Bladder. In Pathology oncology research : POR, 26, 411-418. doi:10.1007/s12253-018-0524-3. https://pubmed.ncbi.nlm.nih.gov/30382527/

6. Cai, Min, Tan, Rukeng, Huang, Yunyi, Guo, Kaixin, Xu, Meng. 2021. High Expression of Tomm34 and Its Correlations With Clinicopathology in Oral Squamous Cell Carcinoma. In Pathology oncology research : POR, 27, 641042. doi:10.3389/pore.2021.641042. https://pubmed.ncbi.nlm.nih.gov/34257607/

7. Jin, Ping, Jiang, Jingwen, Zhou, Li, Wei, Yuquan, Huang, Canhua. 2022. Disrupting metformin adaptation of liver cancer cells by targeting the TOMM34/ATP5B axis. In EMBO molecular medicine, 14, e16082. doi:10.15252/emmm.202216082. https://pubmed.ncbi.nlm.nih.gov/36321555/

8. Poverennaya, Ekaterina V, Pyatnitskiy, Mikhail A, Dolgalev, Georgii V, Kim, Yan S, Ponomarenko, Elena A. 2023. Exploiting Multi-Omics Profiling and Systems Biology to Investigate Functions of TOMM34. In Biology, 12, . doi:10.3390/biology12020198. https://pubmed.ncbi.nlm.nih.gov/36829477/

9. Aleskandarany, Mohammed A, Negm, Ola H, Rakha, Emad A, Tighe, Patrick J, Ellis, Ian O. 2012. TOMM34 expression in early invasive breast cancer: a biomarker associated with poor outcome. In Breast cancer research and treatment, 136, 419-27. doi:10.1007/s10549-012-2249-4. https://pubmed.ncbi.nlm.nih.gov/23053644/