Local Oxidative Damage in the Soma and Dendrites Quarantines Neuronal Mitochondria at the Site of Insult.
Local Oxidative Damage in the Soma and Dendrites Quarantines Neuronal Mitochondria at the Site of Insult.
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DOI：
10.1016/j.isci.2018.07.015
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发表时间：
2018-08-31
期刊：
影响因子：
5.8
通讯作者：
Götz J
中科院分区：
文献类型：
--
作者：
Grimm A;Cummins N;Götz J
神经元高度依赖于线粒体，但很少有人知道它们如何对局部线粒体氧化损伤作出反应。因此，我们在原代海马培养物中开发了一种方案，该方案将光敏剂mito-KillerRed与荧光生物传感器和可光活化的GFP相结合。我们发现在索马和树突中，神经元通过抑制线粒体来限制损伤区室中源自神经元的活性氧的局部增加和ATP产生的减少。虽然细胞质的索马和树突变得氧化后mito-KillerRed激活，树突更敏感的氧化损伤。重要的是，受损的线粒体表现出运动性和融合性降低，从而避免了氧化在整个神经元中的扩散。这些结果建立了神经元如何管理氧化损伤，并增加了我们对局部氧化损伤后线粒体功能的体树突调节的理解。氧化损伤局部包含在神经元的受损区域，ATP水平仅在索马或树突的受损区域降低，ATP水平在氧化损伤的远端区域增加应激线粒体被破碎，运动性和融合率降低生理学;神经科学;细胞生物学
Neurons are highly dependent on mitochondria, but little is known about how they react to a local mitochondrial oxidative insult. We therefore developed a protocol in primary hippocampal cultures that combines the photosensitizer mito-KillerRed with fluorescent biosensors and photoactivatable GFP. We found in both the soma and dendrites that neurons restrict the local increase in mitochondria-derived reactive oxygen species and the decrease in ATP production to the damaged compartment, by quarantining mitochondria. Although the cytosol of both the soma and dendrites became oxidized after mito-KillerRed activation, dendrites were more sensitive to the oxidative insult. Importantly, the impaired mitochondria exhibited decreased motility and fusion, thereby avoiding the spread of oxidation throughout the neuron. These results establish how neurons manage oxidative damage and increase our understanding about the somatodendritic regulation of mitochondrial functions after a local oxidative insult. An oxidative insult is contained locally to the damaged region of a neuron ATP levels decrease only in the damaged region of the soma or dendrite ATP levels increase in the regions distal to the oxidative insult Stressed mitochondria are fragmented, with a decreased motility and fusion rate Physiology; Neuroscience; Cell Biology
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影响因子：
82.9
作者：
Breckwoldt, Michael;Pfister, Franz M. J.;Misgeld, Thomas
通讯作者：
Misgeld, Thomas
DOI：
10.1083/jcb.201401070
发表时间：
2014-09-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ashrafi G;Schlehe JS;LaVoie MJ;Schwarz TL
通讯作者：
Schwarz TL
影响因子：
16.2
作者：
Pickrell AM;Youle RJ
通讯作者：
Youle RJ
影响因子：
5.3
作者：
Ertuerk, Ali;Wang, Yuanyuan;Sheng, Morgan
通讯作者：
Sheng, Morgan
神经退行性中的活性氧与线粒体动力学之间的相互关系。
影响因子：
11.4
作者：
Hung CH;Cheng SS;Cheung YT;Wuwongse S;Zhang NQ;Ho YS;Lee SM;Chang RC
通讯作者：
Chang RC