Mitochondrial dysfunction is considered one of the hallmarks of ischemia/reperfusion injury. Mitochondria are plastic organelles that undergo continuous biogenesis, fusion, and fission. They can be transferred between cells through tunneling nanotubes (TNTs), dynamic structures that allow the exchange of proteins, soluble molecules, and organelles. Maintaining mitochondrial dynamics is crucial to cell function and survival. The present study aimed to assess the effects of melatonin on mitochondrial dynamics, TNT formation, and mitochondria transfer in HT22 cells exposed to oxygen/glucose deprivation followed by reoxygenation (OGD/R). The results showed that melatonin treatment during the reoxygenation phase reduced mitochondrial reactive oxygen species (ROS) production, improved cell viability, and increased the expression of PGC1α and SIRT3. Melatonin also preserved the expression of the membrane translocase proteins TOM20 and TIM23, and of the matrix protein HSP60, which are involved in mitochondrial biogenesis. Moreover, it promoted mitochondrial fusion and enhanced the expression of MFN2 and OPA1. Remarkably, melatonin also fostered mitochondrial transfer between injured HT22 cells through TNT connections. These results provide new insights into the effect of melatonin on mitochondrial network reshaping and cell survival. Fostering TNTs formation represents a novel mechanism mediating the protective effect of melatonin in ischemia/reperfusion injury.

中文翻译：

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褪黑激素重塑线粒体网络并在海马 HT22 细胞缺血样损伤后通过隧道纳米管促进细胞间线粒体转移

线粒体功能障碍被认为是缺血/再灌注损伤的标志之一。线粒体是一种塑料细胞器，可以进行连续的生物发生、融合和裂变。它们可以通过隧道纳米管 (TNT)、允许蛋白质、可溶性分子和细胞器交换的动态结构在细胞之间转移。维持线粒体动力学对细胞功能和存活至关重要。本研究旨在评估褪黑激素对暴露于缺氧/葡萄糖剥夺然后再充氧 (OGD/R) 的 HT22 细胞中线粒体动力学、TNT 形成和线粒体转移的影响。结果表明，在复氧阶段褪黑激素处理减少了线粒体活性氧 (ROS) 的产生，提高了细胞活力，并增加了 PGC1α 和 SIRT3 的表达。褪黑激素还保留了膜转位酶蛋白 TOM20 和 TIM23 以及基质蛋白 HSP60 的表达，这些蛋白与线粒体生物发生有关。此外，它促进线粒体融合并增强 MFN2 和 OPA1 的表达。值得注意的是，褪黑激素还通过 TNT 连接促进了受损 HT22 细胞之间的线粒体转移。这些结果为褪黑激素对线粒体网络重塑和细胞存活的影响提供了新的见解。促进 TNTs 的形成代表了一种介导褪黑激素在缺血/再灌注损伤中的保护作用的新机制。它促进线粒体融合并增强MFN2和OPA1的表达。值得注意的是，褪黑激素还通过 TNT 连接促进了受损 HT22 细胞之间的线粒体转移。这些结果为褪黑激素对线粒体网络重塑和细胞存活的影响提供了新的见解。促进 TNTs 的形成代表了一种介导褪黑激素在缺血/再灌注损伤中的保护作用的新机制。它促进线粒体融合并增强MFN2和OPA1的表达。值得注意的是，褪黑激素还通过 TNT 连接促进了受损 HT22 细胞之间的线粒体转移。这些结果为褪黑激素对线粒体网络重塑和细胞存活的影响提供了新的见解。促进 TNTs 的形成代表了一种介导褪黑激素在缺血/再灌注损伤中的保护作用的新机制。