Iron-induced generation of mitochondrial ROS depends on AMPK activity

Deregulated iron homeostasis is generally believed to be implicated in neurodegenerative diseases, including Parkinson's disease. Nevertheless, it is not fully understood how iron overload can elicit neuronal cell damage. Here we examined mitochondrial reactive oxygen species (ROS) levels in human dopaminergic neuroblastoma SH-SY5Y cells upon iron exposure. A relatively high concentration of iron could significantly increase mitochondrial ROS levels in SH-SY5Y cells. Pharmacological activation of AMP-activated protein kinase (AMPK) almost completely inhibited the effect of iron on mitochondrial ROS. By contrast, AMPK inhibition aggravated the neurotoxicity of iron and enhanced the production of mitochondrial ROS. Collectively, these findings suggested that excess iron may be able to perturb mitochondrial function, and AMPK activity is important for the association of iron and mitochondria.

铁稳态失调通常被认为与包括帕金森病在内的神经退行性疾病有关。然而，铁过载如何引发神经元细胞损伤尚未完全清楚。在此我们检测了人多巴胺能神经母细胞瘤SH - SY5Y细胞在铁暴露后的线粒体活性氧（ROS）水平。较高浓度的铁可显著增加SH - SY5Y细胞中的线粒体ROS水平。AMP活化蛋白激酶（AMPK）的药理激活几乎完全抑制了铁对线粒体ROS的影响。相比之下，AMPK抑制加重了铁的神经毒性并增强了线粒体ROS的产生。总之，这些发现表明过量的铁可能会扰乱线粒体功能，并且AMPK活性对于铁和线粒体的关联很重要。