Mitochondrial Flash: Integrative Reactive Oxygen Species and pH Signals in Cell and Organelle Biology.

Mitochondrial Flash: Integrative Reactive Oxygen Species and pH Signals in Cell and Organelle Biology.
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线粒体闪光:细胞和细胞器生物学中的综合活性氧和 pH 信号

DOI:
10.1089/ars.2016.6739
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发表时间:
2016-09-20
影响因子:
6.6
通讯作者:
Sheu SS
Sheu SS
中科院分区:
生物学2区
文献类型:
--
作者:
Wang W;Gong G;Wang X;Wei-LaPierre L;Cheng H;Dirksen R;Sheu SS

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摘要意义:线粒体研究的最新突破已经推进,重塑和彻底改变了我们对线粒体在健康和疾病中的作用的看法。这些发现包括探索线粒体生物学的新工具的开发,线粒体功能蛋白的分子鉴定,以及线粒体功能调节的新概念和机制的出现。“线粒体闪光”活动的发现不仅为活细胞中单个线粒体氧化还原和pH动态的实时可视化提供了独特的见解,而且还促进了对体内线粒体功能的兴奋性,自主性和整合的理解。最新进展:线粒体闪光是一个短暂的和随机的事件,局限于一个单独的线粒体,并在广泛的生物体中观察到从植物到秀丽隐杆线虫到哺乳动物。由于闪存事件涉及闪存内的多个瞬时并发变化(例如,超氧化物、pH和膜电位),许多不同的线粒体靶向荧光指示剂可以检测闪光活性。越来越多的证据表明,闪光事件反映了一个间歇性的线粒体过程所产生的线粒体呼吸链活动与线粒体渗透性转换孔的瞬时开放的综合快照。关键问题:我们回顾了闪光发现的历史,总结了目前对闪光生物学的理解,突出了关于超氧化物和pH信号在闪光事件中的相对作用的争议,并提出了这两个信号在闪光成因的整合。未来方向:使用闪光作为生物标志物并确定其在细胞信号传导途径中的作用的研究将推动该领域的发展。抗氧化剂。氧化还原信号。25,534-549。
Abstract Significance: Recent breakthroughs in mitochondrial research have advanced, reshaped, and revolutionized our view of the role of mitochondria in health and disease. These discoveries include the development of novel tools to probe mitochondrial biology, the molecular identification of mitochondrial functional proteins, and the emergence of new concepts and mechanisms in mitochondrial function regulation. The discovery of “mitochondrial flash” activity has provided unique insights not only into real-time visualization of individual mitochondrial redox and pH dynamics in live cells but has also advanced understanding of the excitability, autonomy, and integration of mitochondrial function in vivo. Recent Advances: The mitochondrial flash is a transient and stochastic event confined within an individual mitochondrion and is observed in a wide range of organisms from plants to Caenorhabditis elegans to mammals. As flash events involve multiple transient concurrent changes within the mitochondrion (e.g., superoxide, pH, and membrane potential), a number of different mitochondrial targeted fluorescent indicators can detect flash activity. Accumulating evidence indicates that flash events reflect integrated snapshots of an intermittent mitochondrial process arising from mitochondrial respiration chain activity associated with the transient opening of the mitochondrial permeability transition pore. Critical Issues: We review the history of flash discovery, summarize current understanding of flash biology, highlight controversies regarding the relative roles of superoxide and pH signals during a flash event, and bring forth the integration of both signals in flash genesis. Future Directions: Investigations using flash as a biomarker and establishing its role in cell signaling pathway will move the field forward. Antioxid. Redox Signal. 25, 534–549.
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期刊: NATURE MEDICINE
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