A reciprocal relationship between reactive oxygen species and mitochondrial dynamics in neurodegeneration.
A reciprocal relationship between reactive oxygen species and mitochondrial dynamics in neurodegeneration.
复制标题
神经退行性中的活性氧与线粒体动力学之间的相互关系。
DOI：
10.1016/j.redox.2017.08.010
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发表时间：
2018-04
期刊：
影响因子：
11.4
通讯作者：
Chang RC
中科院分区：
文献类型：
--
作者：
Hung CH;Cheng SS;Cheung YT;Wuwongse S;Zhang NQ;Ho YS;Lee SM;Chang RC
由于分裂/融合失衡导致的线粒体碎片化通常与神经变性中的线粒体功能障碍和细胞凋亡有关。通常认为，一旦线粒体形态从其生理管状形式转变，线粒体就变得有缺陷，并且下游凋亡信号传导途径被触发。然而，我们的研究表明，β-淀粉样蛋白（Aβ）诱导线粒体的形态变化，它们变成颗粒状，在形态和功能方面与碎片化的线粒体不同。线粒体活性氧的积累触发颗粒状线粒体的形成，而mitoTEMPO（一种靶向超氧化物清除剂）恢复了Aβ处理的神经元内的管状线粒体形态。有趣的是，通过遗传和药理学工具对线粒体分裂和融合的调节不仅减弱了颗粒线粒体的诱导，还减弱了Aβ处理的神经元中线粒体超氧化物水平。我们的研究显示了线粒体动力学和活性氧之间的相互关系，并在神经退行性疾病发病机制的早期阶段提供了一个新的潜在治疗靶点。Aβ在神经变性的早期阶段诱导颗粒状线粒体。线粒体ROS触发异常的线粒体动力学&颗粒状线粒体。颗粒状线粒体是可逆的，并被mitoTEMPO减弱。线粒体动力学的操纵消除了颗粒线粒体的形成，但也降低了线粒体中的超氧化物水平。线粒体动力学的操纵降低了线粒体中的超氧化物水平。
Mitochondrial fragmentation due to fission/fusion imbalance has often been linked to mitochondrial dysfunction and apoptosis in neurodegeneration. Conventionally, it is believed that once mitochondrial morphology shifts away from its physiological tubular form, mitochondria become defective and downstream apoptotic signaling pathways are triggered. However, our study shows that beta-amyloid (Aβ) induces morphological changes in mitochondria where they become granular-shaped and are distinct from fragmented mitochondria in terms of both morphology and functions. Accumulation of mitochondrial reactive oxygen species triggers granular mitochondria formation, while mitoTEMPO (a mitochondria-targeted superoxide scavenger) restores tubular mitochondrial morphology within Aβ-treated neurons. Interestingly, modulations of mitochondria fission and fusion by genetic and pharmacological tools attenuated not only the induction of granular mitochondria, but also mitochondrial superoxide levels in Aβ−treated neurons. Our study shows a reciprocal relationship between mitochondrial dynamics and reactive oxygen species and provides a new potential therapeutic target at early stages of neurodegenerative disease pathogenesis. Aβ induces granular mitochondria at early stages of neurodegeneration. Mitochondrial ROS triggers aberrant mitochondrial dynamics & granular mitochondria. Granular mitochondria is reversible and attenuated by mitoTEMPO. Manipulation of mitochondrial dynamics abolishes formation of granular mitochondria, but also reduces super oxide levels in mitochondria. Manipulation of mitochondrial dynamics reduces super oxide levels in mitochondria.
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影响因子：
3.7
作者：
Cha MY;Han SH;Son SM;Hong HS;Choi YJ;Byun J;Mook-Jung I
通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
11.4
作者：
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通讯作者：
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