Superoxide flashes in single mitochondria.
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.
Wang
Wang
W
Laboratories of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. wangwang@umich.edu
Fang
Huaqiang
H
Groom
Linda
L
Cheng
Aiwu
A
Zhang
Wanrui
W
Liu
Jie
J
Wang
Xianhua
X
Li
Kaitao
K
Han
Peidong
P
Zheng
Ming
M
Yin
Jinhu
J
Wang
Weidong
W
Mattson
Mark P
MP
Kao
Joseph P Y
JP
Lakatta
Edward G
EG
Sheu
Shey-Shing
SS
Ouyang
Kunfu
K
Chen
Ju
J
Dirksen
Robert T
RT
Cheng
Heping
H
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D032342:Muscle Cells / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D008164:Luminescent Proteins; D017382:Reactive Oxygen Species; D013481:Superoxides