西亚试剂：Superoxide Flashes in Single Mitochondria

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

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