title: Superoxide flashes in single mitochondria.
abstract: 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.
authors.affiliation: Laboratories of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. wangwang@umich.edu
authors.forename: Wang
authors.initials: W
authors.lastname: Wang
authors.forename: Huaqiang
authors.initials: H
authors.lastname: Fang
authors.forename: Linda
authors.initials: L
authors.lastname: Groom
authors.forename: Aiwu
authors.initials: A
authors.lastname: Cheng
authors.forename: Wanrui
authors.initials: W
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Xianhua
authors.initials: X
authors.lastname: Wang
authors.forename: Kaitao
authors.initials: K
authors.lastname: Li
authors.forename: Peidong
authors.initials: P
authors.lastname: Han
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
authors.forename: Jinhu
authors.initials: J
authors.lastname: Yin
authors.forename: Weidong
authors.initials: W
authors.lastname: Wang
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
authors.forename: Joseph P Y
authors.initials: JP
authors.lastname: Kao
authors.forename: Edward G
authors.initials: EG
authors.lastname: Lakatta
authors.forename: Shey-Shing
authors.initials: SS
authors.lastname: Sheu
authors.forename: Kunfu
authors.initials: K
authors.lastname: Ouyang
authors.forename: Ju
authors.initials: J
authors.lastname: Chen
authors.forename: Robert T
authors.initials: RT
authors.lastname: Dirksen
authors.forename: Heping
authors.initials: H
authors.lastname: Cheng
mesh_terms: 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*
chemical_list: D008164:Luminescent Proteins; D017382:Reactive Oxygen Species; D013481:Superoxides