Instituto de Biotecnología y Biomedicina (Biotecmed), Universitat de València, 46100 València, Spain.
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universitat de València, 46100 València, Spain.
Int J Mol Sci. 2022 Jan 24;23(3):1284. doi: 10.3390/ijms23031284.
The eukaryotic translation initiation factor 5A (eIF5A) is an evolutionarily conserved protein that binds ribosomes to facilitate the translation of peptide motifs with consecutive prolines or combinations of prolines with glycine and charged amino acids. It has also been linked to other molecular functions and cellular processes, such as nuclear mRNA export and mRNA decay, proliferation, differentiation, autophagy, and apoptosis. The growing interest in eIF5A relates to its association with the pathogenesis of several diseases, including cancer, viral infection, and diabetes. It has also been proposed as an anti-aging factor: its levels decay in aged cells, whereas increasing levels of active eIF5A result in the rejuvenation of the immune and vascular systems and improved brain cognition. Recent data have linked the role of eIF5A in some pathologies with its function in maintaining healthy mitochondria. The eukaryotic translation initiation factor 5A is upregulated under respiratory metabolism and its deficiency reduces oxygen consumption, ATP production, and the levels of several mitochondrial metabolic enzymes, as well as altering mitochondria dynamics. However, although all the accumulated data strongly link eIF5A to mitochondrial function, the precise molecular role and mechanisms involved are still unknown. In this review, we discuss the findings linking eIF5A and mitochondria, speculate about its role in regulating mitochondrial homeostasis, and highlight its potential as a target in diseases related to energy metabolism.
真核翻译起始因子 5A（eIF5A）是一种进化上保守的蛋白质，它与核糖体结合，促进连续脯氨酸或脯氨酸与甘氨酸和带电荷氨基酸组合的肽基序的翻译。它还与其他分子功能和细胞过程相关联，如核 mRNA 输出和 mRNA 降解、增殖、分化、自噬和细胞凋亡。人们对 eIF5A 的兴趣日益增加，与其在几种疾病的发病机制中的关联有关，包括癌症、病毒感染和糖尿病。它也被提议作为一种抗衰老因子：其水平在衰老细胞中下降，而活性 eIF5A 水平的增加导致免疫和血管系统的年轻化以及大脑认知能力的提高。最近的数据将 eIF5A 在某些病理中的作用与其在维持健康线粒体中的功能联系起来。真核翻译起始因子 5A 在呼吸代谢下上调，其缺乏会降低耗氧量、ATP 产生和几种线粒体代谢酶的水平，并改变线粒体动力学。然而，尽管所有累积的数据都强烈地将 eIF5A 与线粒体功能联系起来，但它所涉及的精确分子作用和机制仍不清楚。在这篇综述中，我们讨论了将 eIF5A 与线粒体联系起来的研究结果，推测了它在调节线粒体稳态中的作用，并强调了它作为与能量代谢相关疾病的靶点的潜力。
