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:

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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/

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