Instituto Biotecmed, Facultad de Ciencias Biológicas, Universitat de València, C/Dr. Moliner 50, E46100 Burjassot, Spain.
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universitat de València, C/Dr. Moliner 50, E46100 Burjassot, Spain.
Int J Mol Sci. 2020 Dec 28;22(1):219. doi: 10.3390/ijms22010219.
Translation elongation factor eIF5A binds to ribosomes to promote peptide bonds between problematic amino acids for the reaction like prolines. eIF5A is highly conserved and essential in eukaryotes, which usually contain two similar but differentially expressed paralogue genes. The human eIF5A-1 isoform is abundant and implicated in some cancer types; the eIF5A-2 isoform is absent in most cells but becomes overexpressed in many metastatic cancers. Several reports have connected eIF5A and mitochondria because it co-purifies with the organelle or its inhibition reduces respiration and mitochondrial enzyme levels. However, the mechanisms of eIF5A mitochondrial function, and whether eIF5A expression is regulated by the mitochondrial metabolism, are unknown. We analysed the expression of yeast eIF5A isoforms Tif51A and Tif51B under several metabolic conditions and in mutants. The depletion of Tif51A, but not Tif51B, compromised yeast growth under respiration and reduced oxygen consumption. Tif51A expression followed dual positive regulation: by high glucose through TORC1 signalling, like other translation factors, to promote growth and by low glucose or non-fermentative carbon sources through Snf1 and heme-dependent transcription factor Hap1 to promote respiration. Upon iron depletion, Tif51A was down-regulated and Tif51B up-regulated. Both were Hap1-dependent. Our results demonstrate eIF5A expression regulation by cellular metabolic status.
翻译延伸因子 eIF5A 与核糖体结合，以促进脯氨酸等反应中存在问题的氨基酸之间形成肽键。eIF5A 在真核生物中高度保守且必不可少，真核生物通常包含两个相似但表达不同的基因。人类 eIF5A-1 同工型丰富，与某些癌症类型有关；eIF5A-2 同工型在大多数细胞中不存在，但在许多转移性癌症中过度表达。有几项报道将 eIF5A 与线粒体联系起来，因为它与细胞器共纯化或其抑制作用降低了呼吸和线粒体酶的水平。然而，eIF5A 在线粒体功能中的机制以及 eIF5A 的表达是否受线粒体代谢调节尚不清楚。我们分析了酵母 eIF5A 同工型 Tif51A 和 Tif51B 在几种代谢条件下以及在突变体中的表达。Tif51A 的耗尽，而不是 Tif51B 的耗尽，会削弱酵母在呼吸作用下的生长能力，并降低耗氧量。Tif51A 的表达受到双重正调控：高葡萄糖通过 TORC1 信号转导，与其他翻译因子一样，促进生长；低葡萄糖或非发酵碳源通过 Snf1 和血红素依赖性转录因子 Hap1 促进呼吸。铁耗竭时，Tif51A 下调，Tif51B 上调。两者都依赖于 Hap1。我们的结果表明 eIF5A 的表达受细胞代谢状态的调节。
