Protons Trigger Mitochondrial Flashes.
Protons Trigger Mitochondrial Flashes.
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DOI：
10.1016/j.bpj.2016.05.052
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发表时间：
2016-07
影响因子：
3.4
通讯作者：
Xianhua Wang;Xing Zhang;Zhanglong Huang;Di Wu;Beibei Liu;Rufeng Zhang;Rongkang Yin;Tingting Hou-Tingti
中科院分区：
文献类型：
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作者：
Xianhua Wang;Xing Zhang;Zhanglong Huang;Di Wu;Beibei Liu;Rufeng Zhang;Rongkang Yin;Tingting Hou-Tingti
新出现的证据表明，线粒体闪光（mitoflashes）是高度保守的基本线粒体信号事件。然而，哪种信号控制它们的点火以及它们如何与其他线粒体信号和功能整合仍然难以捉摸。在这项研究中，我们的目的是进一步描绘的mitoflash的信号成分，并确定mitoflash触发机制。使用多个生物传感器和化学探针以及无标记的自发荧光，我们发现，mitoflash反映了化学和电激发在单细胞器水平，包括突发超氧化物的产生，氧化的氧化还原位移，和基质碱化以及瞬时膜去极化。电中性H+/K+或H+/Na+反向转运和基质质子释放在心肌细胞和HeLa细胞中引起了广泛的动态范围内的即时和强大的mitoflash反应。然而，电荷补偿质子运输，去极化线粒体，造成相反的效果，和稳定的基质酸化轻度抑制mitoflashes。基于数值模拟，我们估计的平均质子寿命为1.42 ns和扩散距离为2.06 nm的矩阵。我们的结论是，纳米结构域质子作为一种新的，据我们所知，在充满活力的线粒体mitoflashes触发。这一发现表明，mitoflash的成因是功能和机制与线粒体能量代谢。
Emerging evidence indicates that mitochondrial flashes (mitoflashes) are highly conserved elemental mitochondrial signaling events. However, which signal controls their ignition and how they are integrated with other mitochondrial signals and functions remain elusive. In this study, we aimed to further delineate the signal components of the mitoflash and determine the mitoflash trigger mechanism. Using multiple biosensors and chemical probes as well as label-free autofluorescence, we found that the mitoflash reflects chemical and electrical excitation at the single-organelle level, comprising bursting superoxide production, oxidative redox shift, and matrix alkalinization as well as transient membrane depolarization. Both electroneutral H+/K+or H+/Na+antiport and matrix proton uncaging elicited immediate and robust mitoflash responses over a broad dynamic range in cardiomyocytes and HeLa cells. However, charge-uncompensated proton transport, which depolarizes mitochondria, caused the opposite effect, and steady matrix acidification mildly inhibited mitoflashes. Based on a numerical simulation, we estimated a mean proton lifetime of 1.42 ns and diffusion distance of 2.06 nm in the matrix. We conclude that nanodomain protons act as a novel, to our knowledge, trigger of mitoflashes in energized mitochondria. This finding suggests that mitoflash genesis is functionally and mechanistically integrated with mitochondrial energy metabolism.