Imaging superoxide flash and metabolism-coupled mitochondrial permeability transition in living animals
Imaging superoxide flash and metabolism-coupled mitochondrial permeability transition in living animals
复制标题
活体动物中超氧化物闪现和代谢耦合线粒体通透性转变的成像
DOI：
10.1038/cr.2011.81
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发表时间：
2011-09-01
期刊：
影响因子：
44.1
通讯作者：
Cheng, Heping
中科院分区：
文献类型：
--
作者：
Fang, Huaqiang;Chen, Min;Cheng, Heping
线粒体对能量代谢和活性氧（ROS）的产生至关重要。在完整细胞中，呼吸线粒体表现出自发的“超氧化物闪光”，这是瞬时线粒体通透性转变（tMPT）的量子ros产生事件。在这里，我们首次在表达超氧化物生物传感器mt-cpYFP的活小鼠中进行线粒体超氧化物闪烁和tMPT活性的体内成像，并证明它们与全身葡萄糖代谢的耦合。麻醉转基因小鼠的骨骼肌和坐骨神经中出现了强大的tMPT/超氧化物闪变活性。在骨骼肌中，成像tMPT/超氧化物闪光灯揭示了线粒体迷宫般的三维网络，这些网络同步运作。tMPT/超氧化物闪变活性在响应全身性葡萄糖挑战或胰岛素刺激时激增，以明显的频率调制方式，也涉及tMPT门控模式的转变。因此，tmpt依赖性线粒体ROS信号的体内成像和代谢- tmpt -超氧化物闪偶联的发现标志着线粒体功能和ROS信号在健康和疾病中的研究取得了重要的技术和概念进展。
The mitochondrion is essential for energy metabolism and production of reactive oxygen species (ROS). In intact cells, respiratory mitochondria exhibit spontaneous "superoxide flashes", the quantal ROS-producing events consequential to transient mitochondrial permeability transition (tMPT). Here we perform the first in vivo imaging of mitochondrial superoxide flashes and tMPT activity in living mice expressing the superoxide biosensor mt-cpYFP, and demonstrate their coupling to whole-body glucose metabolism. Robust tMPT/superoxide flash activity occurred in skeletal muscle and sciatic nerve of anesthetized transgenic mice. In skeletal muscle, imaging tMPT/superoxide flashes revealed labyrinthine three-dimensional networks of mitochondria that operate synchronously. The tMPT/superoxide flash activity surged in response to systemic glucose challenge or insulin stimulation, in an apparently frequency-modulated manner and involving also a shift in the gating mode of tMPT. Thus, in vivo imaging of tMPT-dependent mitochondrial ROS signals and the discovery of the metabolism-tMPT-superoxide flash coupling mark important technological and conceptual advances for the study of mitochondrial function and ROS signaling in health and disease.