The eukaryotic translation initiation factor 5A (eIF5A) is the only known protein containing the amino acid residue hypusine, essential for its activity. Hypusine residue is produced by a posttranslational modification involving deoxyhypusine synthetase and deoxyhypusine hydroxylase. Herein, we aimed to describe the role of the alternative human isoform A on mitochondrial processes. Isoform A depletion modulates oxidative metabolism in association with the downregulation of mitochondrial biogenesis‐related genes. Through positive feedback, it increases cell respiration leading to highly reactive oxygen species production, which impacts mitochondrial bioenergetics. These metabolic changes compromise mitochondrial morphology, increasing its electron density and fission, observed by transmission electron microscopy. This set of changes leads the cells to apoptosis, evidenced by increased DNA fragmentation and proapoptotic BAK protein content increase. Thus, we show that the alternative eIF5A isoform A is crucial for energy metabolism controlled by mitochondria and cellular survival.

中文翻译：

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替代的人类 eIF5A 蛋白同种型在线粒体中起关键作用

真核翻译起始因子 5A (eIF5A) 是唯一已知的含有氨基酸残基 hypusine 的蛋白质，对其活性至关重要。Hypusine 残基由涉及脱氧hypusine 合成酶和脱氧hypusine 羟化酶的翻译后修饰产生。在此，我们旨在描述替代人类亚型 A 在线粒体过程中的作用。同工型 A 消耗调节氧化代谢与线粒体生物发生相关基因的下调相关。通过正反馈，它增加细胞呼吸，导致高活性氧的产生，从而影响线粒体生物能学。通过透射电子显微镜观察到，这些代谢变化会损害线粒体形态，增加其电子密度和裂变。这组变化导致细胞凋亡，DNA 断裂增加和促凋亡 BAK 蛋白含量增加证明了这一点。因此，我们表明替代的 eIF5A 同种型 A 对于由线粒体和细胞存活控制的能量代谢至关重要。