Sorianello Eleonora, Katz Maximiliano J, Acevedo Julieta M, Melani Mariana, Perez-Perri Joel I, Wappner Pablo
Laboratorio de Regulación Hipofisaria, Instituto de Biología y Medicina Experimental (IBYME CONICET), Vuelta de Obligado 2490, Buenos Aires, 1428, Argentina.
Departamento de Ciencias Fisiológicas, Facultad de Medicina, Universidad de Buenos Aires, Paraguay, 2155, Buenos Aires, 1121, Argentina.
Sci Rep. 2025 Jul 2;15(1):23370. doi: 10.1038/s41598-025-94457-5.
Adaptation to hypoxia requires the activation of concerted cellular mechanisms mainly dependent on the transcription factor HIF/Sima. 4E-BP/Thor is a CAP-dependent translation inhibitor involved in several cellular and developmental processes, which has been previously shown to be required for adaptation to starvation and oxidative stress. In this work, we show that 4E-BP/Thor is transcriptionally induced in Drosophila upon exposure to hypoxia in a Sima- and Foxo-dependent manner, and that loss of function of 4E-BP/Thor compromises fly survival in hypoxia. In Thor loss-of-function flies, alterations of mitochondria in the indirect flight muscle occur, and reactive oxygen species (ROS) accumulate, leading to premature lethality in hypoxia. These results highlight the importance of the translational regulator Thor in fly adaptation to hypoxia, presumably by contributing to maintain normal mitochondrial function, and preventing ROS accumulation in low oxygen conditions.
适应缺氧需要激活主要依赖于转录因子HIF/Sima的协同细胞机制。4E-BP/Thor是一种依赖CAP的翻译抑制剂，参与多个细胞和发育过程，先前已证明其对适应饥饿和氧化应激是必需的。在这项研究中，我们发现果蝇在暴露于缺氧环境时，4E-BP/Thor会以依赖Sima和Foxo的方式被转录诱导，并且4E-BP/Thor功能丧失会损害果蝇在缺氧环境中的生存能力。在Thor功能丧失的果蝇中，间接飞行肌中的线粒体发生改变，活性氧（ROS）积累，导致在缺氧环境中过早死亡。这些结果凸显了翻译调节因子Thor在果蝇适应缺氧过程中的重要性，推测是通过有助于维持正常的线粒体功能以及防止在低氧条件下ROS积累来实现的。
