Mitochondrial redox and pH signaling occurs in axonal and synaptic organelle clusters.
Mitochondrial redox and pH signaling occurs in axonal and synaptic organelle clusters.
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DOI：
10.1038/srep23251
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发表时间：
2016-03-22
影响因子：
4.6
通讯作者：
Kurz FT
中科院分区：
文献类型：
--
作者：
Breckwoldt MO;Armoundas AA;Aon MA;Bendszus M;O'Rourke B;Schwarzländer M;Dick TP;Kurz FT
氧化还原开关是肿瘤、心血管和神经系统疾病的重要介质。最近，我们发现自发的氧化还原信号在神经元中的单电子水平的谷胱甘肽氧化的瞬变去沿着缩短和再伸长的细胞器。我们现在已经开发出先进的图像和信号处理方法来重新评估和扩展以前获得的数据。在这里，我们分析整个线粒体群体的氧化还原和pH信号。总的来说，我们使用光学传感器（mito-Grx 1-roGFP 2; mito-SypHer）量化了1797个来自肋间轴突和神经肌肉突触的线粒体中628个氧化还原和pH事件的影响。我们发现，神经元线粒体可以经历多个氧化还原循环表现出显着不同的信号特征相比，单一的氧化还原事件。氧化还原和pH事件更常发生在线粒体簇中（中等簇大小：34.1 ± 4.8 μm2）。局部簇具有较高的线粒体密度比其余的轴突，这表明形态和功能线粒体间耦合。我们发现簇的形成是氧化还原敏感的，可以被抗氧化剂MitoQ阻断。在神经挤压范例中，线粒体簇在损伤部位附近顺序形成，并且氧化在线粒体之间扩散。我们的方法结合了光学生物能量学和先进的信号处理，并允许对整个线粒体群体进行定量评估。
Redox switches are important mediators in neoplastic, cardiovascular and neurological disorders. We recently identified spontaneous redox signals in neurons at the single mitochondrion level where transients of glutathione oxidation go along with shortening and re-elongation of the organelle. We now have developed advanced image and signal-processing methods to re-assess and extend previously obtained data. Here we analyze redox and pH signals of entire mitochondrial populations. In total, we quantified the effects of 628 redox and pH events in 1797 mitochondria from intercostal axons and neuromuscular synapses using optical sensors (mito-Grx1-roGFP2; mito-SypHer). We show that neuronal mitochondria can undergo multiple redox cycles exhibiting markedly different signal characteristics compared to single redox events. Redox and pH events occur more often in mitochondrial clusters (medium cluster size: 34.1 ± 4.8 μm2). Local clusters possess higher mitochondrial densities than the rest of the axon, suggesting morphological and functional inter-mitochondrial coupling. We find that cluster formation is redox sensitive and can be blocked by the antioxidant MitoQ. In a nerve crush paradigm, mitochondrial clusters form sequentially adjacent to the lesion site and oxidation spreads between mitochondria. Our methodology combines optical bioenergetics and advanced signal processing and allows quantitative assessment of entire mitochondrial populations.