Zn2+ inhibits mitochondrial movement in neurons by phosphatidylinositol 3-kinase activation
Zn2+ inhibits mitochondrial movement in neurons by phosphatidylinositol 3-kinase activation
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DOI：
10.1523/jneurosci.0868-05.2005
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发表时间：
2005-10-12
影响因子：
5.3
通讯作者：
Reynolds, IJ
中科院分区：
文献类型：
--
作者：
Malaiyandi, LM;Honick, AS;Reynolds, IJ
线粒体已被确定为锌神经毒性作用的目标，可能是通过减少线粒体能量产生和增加活性氧积累来实现的。据推测，线粒体运输受损可能是神经元损伤的机制。在这里，我们报告神经元内锌的升高会损害线粒体运输。在足以造成损伤的浓度下，锌迅速抑制线粒体运动而不改变形态。锌螯合最初恢复了运动，但锌的作用在 10 分钟内变得对螯合剂不敏感。对下游信号事件的研究表明，磷脂酰肌醇 (PI) 3-激酶抑制剂可阻止锌对运动的影响。此外，PI 3-激酶的瞬时抑制提供了针对锌介导的毒性的神经保护作用。这些数据说明了调节神经元线粒体运输的新机制，并且还表明线粒体运输可能与神经元活力密切相关。
Mitochondria have been identified as targets of the neurotoxic actions of zinc, possibly through decreased mitochondrial energy production and increased reactive oxygen species accumulation. It has been hypothesized that impairment of mitochondrial trafficking may be a mechanism of neuronal injury. Here, we report that elevated intraneuronal zinc impairs mitochondrial trafficking. At concentrations just sufficient to cause injury, zinc rapidly inhibited mitochondrial movement without altering morphology. Zinc chelation initially restored movement, but the actions of zinc became insensitive to chelator in < 10 min. A search for downstream signaling events revealed that inhibitors of phosphatidylinositol ( PI) 3-kinase prevented this zinc effect on movement. Moreover, transient inhibition of PI 3-kinase afforded neuroprotection against zinc-mediated toxicity. These data illustrate a novel mechanism that regulates mitochondrial trafficking in neurons and also suggest that mitochondrial trafficking may be closely coupled to neuronal viability.