Abstract：
Embryonic stem cells (ESCs) exhibit a metabolic preference for glycolysis over oxidative phosphorylation to meet their substantial adenosine triphosphate (ATP) demands during self-renewal. This metabolic choice inherently maintains low mitochondrial activity and minimal reactive oxygen species (ROS) generation. Nonetheless, the intricate molecular mechanisms governing the restraint of ROS production and the mitigation of cellular damage remain incompletely elucidated. In this study, we reveal the pivotal role of RNA-binding motif protein 46 (RBM46) in ESCs, acting as a direct post transcriptional regulator of ROS levels by modulating BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (Bnip3) mRNA expression. Rbm46 knockout lead to diminished mitochondrial autophagy, culminating in elevated ROS within ESCs, disrupting the delicate balance required for healthy self-renewal. These findings provide insights into a novel mechanism governing ROS regulation in ESCs.
摘要：
胚胎干细胞(ESC)表现出糖酵解相对于氧化磷酸化的代谢偏好,以满足其在自我更新期间的大量三磷酸腺苷(ATP)需求。这种代谢选择固有地保持低线粒体活性和最少的活性氧(ROS)产生。尽管如此，抑制ROS产生和减轻细胞损伤的复杂分子机制仍未完全阐明。在这项研究中,我们揭示了RNA结合基序蛋白46（RBM46）在ESCs中的关键作用，通过调节BCL2/腺病毒E1B19kDa蛋白相互作用蛋白3（Bnip3）mRNA表达，充当ROS水平的直接转录后调节剂。Rbm46敲除导致线粒体自噬减少，最终导致ESC内ROS升高，破坏健康自我更新所需的微妙平衡。这些发现提供了对控制ESC中ROS调节的新机制的见解。
