División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado Postal, 70-253 Ciudad de México, Mexico.
Oxid Med Cell Longev. 2021 Apr 13;2021:8832863. doi: 10.1155/2021/8832863. eCollection 2021.
Reactive oxygen species (ROS) production has been associated with neuronal death. ROS are also involved in mitochondrial fission, which is mediated by Dynamin-related protein 1 (Drp1). The regulation of mitochondrial fragmentation mediated by Drp1 and its relationship to mitochondrial ROS (mtROS) in neuronal death have not been completely clarified. The aim of this study is to evaluate the role of mtROS in cell death and their involvement in the activation of Drp1 and mitochondrial fission in a model of cell death of cultured cerebellar granule neurons (CGN). Neuronal death of CGN induced by potassium deprivation (K5) and staurosporine (ST) triggers mitochondrial ROS production and mitochondrial fragmentation. K5 condition evoked an increase of Drp1 phosphorylation at Ser616, but ST treatment led to a decrease of Drp1 phosphorylation. Moreover, the death of CGN induced by both K5 and ST was markedly reduced in the presence of MitoTEMPO; however, mitochondrial morphology was not recovered. Here, we show that the mitochondria are the initial source of ROS involved in the neuronal death of CGN and that mitochondrial fragmentation is a common event in cell death; however, this process is not mediated by Drp1 phosphorylation at Ser616.
活性氧（ROS）的产生与神经元死亡有关。ROS 还参与由与 DRP1 相关的蛋白 1（Drp1）介导的线粒体裂变。DRP1 介导的线粒体片段化的调节及其与神经元死亡中线粒体 ROS（mtROS）的关系尚未完全阐明。本研究旨在评估 mtROS 在细胞死亡中的作用及其在培养小脑颗粒神经元（CGN）细胞死亡模型中 Drp1 激活和线粒体裂变中的作用。钾剥夺（K5）和 staurosporine（ST）诱导的 CGN 神经元死亡引发线粒体 ROS 产生和线粒体片段化。K5 条件导致 Drp1 在 Ser616 处的磷酸化增加，但 ST 处理导致 Drp1 磷酸化减少。此外，在 MitoTEMPO 存在下，K5 和 ST 诱导的 CGN 死亡明显减少；然而，线粒体形态没有恢复。在这里，我们表明线粒体是参与 CGN 神经元死亡的 ROS 的初始来源，线粒体片段化是细胞死亡的常见事件；然而，这个过程不是由 Ser616 处的 DRP1 磷酸化介导的。
