Armcx1, also known as Armadillo Repeat Containing X-Linked 1, is a member of the ARM Repeat X-linked protein family. It plays essential roles in regulating mitochondrial transport and dynamics, which is crucial for neuronal survival and axon regeneration. It is also involved in cell cycle and epithelial-mesenchymal transition (EMT) signals through its interaction with c-Myc [1,2,3,5]. The generation of an Armcx1 conditional knockout (CKO) mouse line provides a valuable research model for studying its functions in vivo [4].

In lung adenocarcinoma (LUAD), Armcx1 acts as a tumor suppressor. Its down-regulation in clinical samples is associated with poor prognoses. Overexpression of Armcx1 inhibits LUAD cell growth and metastasis both in vitro and in vivo by recruiting the E3 ubiquitin ligase FBXW7 to mediate ubiquitinated degradation of c-Myc, suppressing its nuclear accumulation [1]. In traumatic brain injury (TBI) models, inhibition of Armcx1 expression in mice leads to impaired mitochondrial transport, abnormal mitochondrial morphology, reduced ATP levels, aggravated neuronal apoptosis, and neurological dysfunction. This indicates that Armcx1 may exert neuroprotective effects through a mitochondrial transport pathway involving Miro1 [2,3]. In a mouse model of experimental intracerebral hemorrhage, Armcx1 overexpression shows protective effects on brain cell death around the hematoma and improves neurobehavioral deficits [6].

In conclusion, Armcx1 is vital for mitochondrial-related functions in neurons and has tumor-suppressing effects in certain cancers. The Armcx1 CKO mouse models have been instrumental in revealing its roles in TBI, intracerebral hemorrhage, and lung adenocarcinoma, providing insights into potential therapeutic approaches for these disease conditions [1,2,3,4,6].

References:

1. Hu, Zhe, Wu, Yilin, Sun, Xiaoou, Qiu, Houkuang, Zhuo, Enqing. 2024. ARMCX1 inhibits lung adenocarcinoma progression by recruiting FBXW7 for c-Myc degradation. In Biology direct, 19, 82. doi:10.1186/s13062-024-00532-8. https://pubmed.ncbi.nlm.nih.gov/39285446/

2. Li, Qiuying, Ni, Haibo, Rui, Qin, Gao, Rong, Shen, Hongbo. 2024. Armcx1 Reduces Neurological Damage Via a Mitochondrial Transport Pathway Involving Miro1 After Traumatic Brain Injury. In Neuroscience, 545, 111-124. doi:10.1016/j.neuroscience.2024.03.009. https://pubmed.ncbi.nlm.nih.gov/38492796/

3. Lu, Dengfeng, Wang, Yi, Liu, Guangjie, Wu, Yu, Wang, Zhong. 2023. Armcx1 attenuates secondary brain injury in an experimental traumatic brain injury model in male mice by alleviating mitochondrial dysfunction and neuronal cell death. In Neurobiology of disease, 184, 106228. doi:10.1016/j.nbd.2023.106228. https://pubmed.ncbi.nlm.nih.gov/37454781/

4. Bright, Cora L, Bomze, Howard M, Bhaumik, Mantu, Cartoni, Romain, Gospe, Sidney M. . Generation of an Armcx1 Conditional Knockout Mouse. In Genesis (New York, N.Y. : 2000), 62, e23615. doi:10.1002/dvg.23615. https://pubmed.ncbi.nlm.nih.gov/39139090/

5. Cartoni, Romain, Norsworthy, Michael W, Bei, Fengfeng, Schwarz, Thomas L, He, Zhigang. . The Mammalian-Specific Protein Armcx1 Regulates Mitochondrial Transport during Axon Regeneration. In Neuron, 92, 1294-1307. doi:10.1016/j.neuron.2016.10.060. https://pubmed.ncbi.nlm.nih.gov/28009275/

6. Xu, Xiaowen, Li, Haiying, Lu, Shiqi, Shen, Yi. 2023. Roles of syntaphilin and armadillo repeat-containing X-linked protein 1 in brain injury after experimental intracerebral hemorrhage. In Neuroscience letters, 809, 137300. doi:10.1016/j.neulet.2023.137300. https://pubmed.ncbi.nlm.nih.gov/37187340/