Instituto de Biotecnología y Biomedicina (Biotecmed), Universitat de València, Spain.
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universitat de València, Spain.
FEBS Lett. 2022 Jul;596(14):1809-1826. doi: 10.1002/1873-3468.14366. Epub 2022 May 25.
Mitochondrial activity adapts to cellular energetic and metabolic demands; its dysfunction is a hallmark of ageing and many human diseases. The evolutionarily conserved translation elongation factor eIF5A is involved in maintaining mitochondrial function. In humans, eIF5A is encoded by two highly homologous but differentially expressed genes; in yeast, these are TIF51A and TIF51B. We show that yeast transcription factor Hap1 constitutively binds to the TIF51A promoter to activate its expression under respiration, but represses its expression under nonrespiration conditions by recruiting the corepressor Tup1. Hap1 indirectly regulates TIF51B expression by binding to and activating the TIF51B repressor genes ROX1 and MOT3 under respiration and repressing them under nonrespiration. Thus, the levels of eIF5A isoforms are adapted to the mitochondrial functional status.
线粒体活性适应细胞能量和代谢需求；其功能障碍是衰老和许多人类疾病的标志。进化上保守的翻译延伸因子 eIF5A 参与维持线粒体功能。在人类中，eIF5A 由两个高度同源但表达不同的基因编码；在酵母中，这些基因是 TIF51A 和 TIF51B。我们表明，酵母转录因子 Hap1 持续结合到 TIF51A 启动子上，在呼吸作用下激活其表达，但通过招募核心抑制剂 Tup1 在非呼吸条件下抑制其表达。Hap1 通过在呼吸作用下结合并激活 TIF51B 抑制子基因 ROX1 和 MOT3 并在非呼吸作用下抑制它们，从而间接调节 TIF51B 的表达。因此，eIF5A 同工型的水平适应于线粒体功能状态。
