Eif5a-KO Mouse

Eif5a, the eukaryotic translation initiation factor 5A, is an evolutionarily conserved protein. It binds ribosomes to facilitate translation of specific peptide motifs and is involved in multiple cellular processes like nuclear mRNA export, mRNA decay, proliferation, and apoptosis [2]. Its function is closely associated with the polyamine spermidine-dependent hypusination pathway, a post-translational modification crucial for its activation [1,4,5,6,7,8,9]. Eif5a is essential for various biological functions and has implications in numerous diseases, making it a significant target for research.

In muscle stem cell (satellite cell, SC) activation, SC-specific eIF5A-knockout (KO) mice revealed that eIF5A is required for spermidine-mediated SC activation by controlling MyoD translation. Depletion of eIF5A in SCs results in impaired muscle regeneration in mice, highlighting its importance in this process [3]. In macrophages, acute inhibition of the polyamine-eIF5A-hypusine axis blunts OXPHOS-dependent alternative activation while leaving aerobic glycolysis-dependent classical activation intact, suggesting a role in macrophage activation regulation [1].

In conclusion, Eif5a plays essential roles in translation, mitochondrial function, cell activation, and differentiation. The use of Eif5a KO mouse models has provided valuable insights into its role in muscle regeneration and macrophage activation, which are relevant to muscular diseases and immunological conditions respectively. These studies enhance our understanding of Eif5a's functions and its potential as a therapeutic target in related diseases.

References:

1. Puleston, Daniel J, Buck, Michael D, Klein Geltink, Ramon I, Balabanov, Stefan, Pearce, Erika L. 2019. Polyamines and eIF5A Hypusination Modulate Mitochondrial Respiration and Macrophage Activation. In Cell metabolism, 30, 352-363.e8. doi:10.1016/j.cmet.2019.05.003. https://pubmed.ncbi.nlm.nih.gov/31130465/

2. Barba-Aliaga, Marina, Alepuz, Paula. 2022. Role of eIF5A in Mitochondrial Function. In International journal of molecular sciences, 23, . doi:10.3390/ijms23031284. https://pubmed.ncbi.nlm.nih.gov/35163207/

3. Zhang, Qianying, Han, Wanhong, Wu, Rimao, Zhang, Yong, Li, Hu. 2024. Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control. In Cell discovery, 10, 94. doi:10.1038/s41421-024-00712-w. https://pubmed.ncbi.nlm.nih.gov/39251577/

4. Gonzalez-Menendez, Pedro, Phadke, Ira, Olive, Meagan E, Kinet, Sandrina, Taylor, Naomi. . Arginine metabolism regulates human erythroid differentiation through hypusination of eIF5A. In Blood, 141, 2520-2536. doi:10.1182/blood.2022017584. https://pubmed.ncbi.nlm.nih.gov/36735910/

5. Zhou, Jin, Pang, Jeremy, Tripathi, Madhulika, Singh, Brijesh Kumar, Yen, Paul Michael. 2022. Spermidine-mediated hypusination of translation factor EIF5A improves mitochondrial fatty acid oxidation and prevents non-alcoholic steatohepatitis progression. In Nature communications, 13, 5202. doi:10.1038/s41467-022-32788-x. https://pubmed.ncbi.nlm.nih.gov/36057633/

6. Guo, Jing-Si, Liu, Kai-Li, Qin, Yu-Xi, Yang, Yue-Hui, Li, Xin-Yang. 2023. Hypusination-induced DHPS/eIF5A pathway as a new therapeutic strategy for human diseases: A mechanistic review and structural classification of DHPS inhibitors. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 167, 115440. doi:10.1016/j.biopha.2023.115440. https://pubmed.ncbi.nlm.nih.gov/37683595/

7. Zhang, Hanlin, Alsaleh, Ghada, Feltham, Jack, Mellor, Jane, Simon, Anna Katharina. 2019. Polyamines Control eIF5A Hypusination, TFEB Translation, and Autophagy to Reverse B Cell Senescence. In Molecular cell, 76, 110-125.e9. doi:10.1016/j.molcel.2019.08.005. https://pubmed.ncbi.nlm.nih.gov/31474573/

8. Li, Hongde, Wu, Bo-Kuan, Kanchwala, Mohammed, Zheng, Yonggang, Pan, Duojia. 2022. YAP/TAZ drives cell proliferation and tumour growth via a polyamine-eIF5A hypusination-LSD1 axis. In Nature cell biology, 24, 373-383. doi:10.1038/s41556-022-00848-5. https://pubmed.ncbi.nlm.nih.gov/35177822/

9. Sfakianos, Aristeidis Panagiotis, Raven, Rebecca Mallory, Willis, Anne Elizabeth. . The pleiotropic roles of eIF5A in cellular life and its therapeutic potential in cancer. In Biochemical Society transactions, 50, 1885-1895. doi:10.1042/BST20221035. https://pubmed.ncbi.nlm.nih.gov/36511302/