活性氧族（reactive oxygen species, ROS）是含氧并具有高反應活性的一類自由基或分子,，其中超氧陰離子是一種高活性氧自由基，并且是細胞內(nèi)ROS的最初生成形式,，廣泛參與細胞信號調(diào)節(jié),、代謝、生存和凋亡,，而氧化應激是衰老和多種重大疾病如心肌梗死,、腦卒中、糖尿病,、老年癡呆癥等重要機制之一,。
在科技部973計劃等的資助下,，北京大學分子醫(yī)學研究所程和平教授研究組與合作者為共同第一作者和共同責任作者的論文“單個線粒體超氧炫”，于7月25日在《細胞》（Cell）雜志以配圖 “Featured Article”形式發(fā)表,。
研究發(fā)現(xiàn)一種新的細胞超氧生成事件,，并命名為“超氧炫”（superoxide flashes）。超氧炫是細胞內(nèi)（含102-104個線粒體）單個線粒體中超氧信號的瞬時爆發(fā)現(xiàn)象,，這是首次在活體細胞中觀測到局部,、間歇性、量子化超氧的產(chǎn)生,。超氧炫為線粒體膜通透性轉(zhuǎn)運孔道(mPTP)開放所觸發(fā),，與線粒體電子傳遞鏈活性密切相關(guān)。上述發(fā)現(xiàn)是基于發(fā)明了一種新穎的高特異性超氧指示劑,，即基因編碼的,、定位于線粒體的可用于實時測量的熒光蛋白。
上述工作對自由基和線粒體研究領(lǐng)域有三方面的意義,，一是找到了新的ROS信號指示劑,，二是超氧炫可作為氧化應激相關(guān)疾病的生物標記物，三是對生理和病理狀況下mPTP和電子傳遞鏈功能有了新認識,。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell,，Vol 134, 279-290，Wang Wang,，Heping Cheng
Superoxide Flashes in Single Mitochondria
Wang Wang,1, Huaqiang Fang,4 Linda Groom,5 Aiwu Cheng,2 Wanrui Zhang,4 Jie Liu,4 Xianhua Wang,4 Kaitao Li,4 Peidong Han,4 Ming Zheng,4 Jinhu Yin,3 Weidong Wang,3 Mark P. Mattson,2 Joseph P.Y. Kao,6 Edward G. Lakatta,1 Shey-Shing Sheu,5 Kunfu Ouyang,7 Ju Chen,7 Robert T. Dirksen,5 and Heping Cheng4,
1 Laboratories of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
2 Neurosciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
3 Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
4 Institute of Molecular Medicine and National Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing 100871, China
5 Department of Pharmacology and Physiology, University of Rochester, School of Medicine and Dentistry, Rochester, NY 14642, USA
6 Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
7 Department of Medicine, University of California, San Diego, CA 92093, USA
Summary
In quiescent cells, mitochondria are the primary source of reactive oxygen species (ROS), which are generated by leakiness of the electron transport chain (ETC). High levels of ROS can trigger cell death, whereas lower levels drive diverse and important cellular functions. We show here by employing a newly developed mitochondrial matrix-targeted superoxide indicator, that individual mitochondria undergo spontaneous bursts of superoxide generation, termed “superoxide flashes.” Superoxide flashes occur randomly in space and time, exhibit all-or-none properties, and provide a vital source of superoxide production across many different cell types. Individual flashes are triggered by transient openings of the mitochondrial permeability transition pore stimulating superoxide production by the ETC. Furthermore, we observe a flurry of superoxide flash activity during reoxygenation of cardiomyocytes after hypoxia, which is inhibited by the cardioprotective compound adenosine. We propose that superoxide flashes could serve as a valuable biomarker for a wide variety of oxidative stress-related diseases.
