Superoxide flashes in single mitochondria

被引:598
作者
Wang, Wang [1 ]
Fang, Huaqiang [4 ,5 ]
Groom, Linda [6 ]
Cheng, Aiwu [2 ]
Zhang, Wanrui [4 ,5 ]
Liu, Jie [4 ,5 ]
Wang, Xianhua [4 ,5 ]
Li, Kaitao [4 ,5 ]
Han, Peidong [4 ,5 ]
Zheng, Ming [4 ,5 ]
Yin, Jinhu [3 ]
Wang, Weidong [3 ]
Mattson, Mark P. [2 ]
Kao, Joseph P. Y. [7 ]
Lakatta, Edward G. [1 ]
Sheu, Shey-Shing [6 ]
Ouyang, Kunfu [8 ]
Chen, Ju [8 ]
Dirksen, Robert T. [6 ]
Cheng, Heping [4 ,5 ]
机构
[1] NIA, NIH, Cardiovasc Sci Lab, Baltimore, MD 21224 USA
[2] NIA, NIH, Neurosci Lab, Baltimore, MD 21224 USA
[3] NIA, NIH, Genet Lab, Baltimore, MD 21224 USA
[4] Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China
[5] Peking Univ, Natl Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China
[6] Univ Rochester, Sch Med & Dent, Dept Pharmacol & Physiol, Rochester, NY 14642 USA
[7] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA
[8] Univ Calif San Diego, Dept Med, San Diego, CA 92093 USA
关键词
D O I
10.1016/j.cell.2008.06.017
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:279 / 290
页数:12
相关论文
共 57 条
[31]   Mitochondrial redox state and Ca2+ sparks in permeabilized mammalian skeletal muscle [J].
Isaeva, EV ;
Shkryl, VA ;
Shirokova, N .
JOURNAL OF PHYSIOLOGY-LONDON, 2005, 565 (03) :855-872
[32]   HUMAN-CELLS LACKING MTDNA - REPOPULATION WITH EXOGENOUS MITOCHONDRIA BY COMPLEMENTATION [J].
KING, MP ;
ATTARDI, G .
SCIENCE, 1989, 246 (4929) :500-503
[33]   The role of oxidative stress in carcinogenesis [J].
Klaunig, JE ;
Kamendulis, LM .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 2004, 44 :239-267
[34]   Reactive species mechanisms of cellular hypoxia-reoxygenation injury [J].
Li, CY ;
Jackson, RM .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2002, 282 (02) :C227-C241
[35]   Structure and dynamics of the mitochondrial inner membrane cristae [J].
Mannella, Carmen A. .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2006, 1763 (5-6) :542-548
[36]   Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-α activation [J].
Mansfield, KD ;
Guzy, RD ;
Pan, Y ;
Young, RM ;
Cash, TP ;
Schumacker, PT ;
Simon, MC .
CELL METABOLISM, 2005, 1 (06) :393-399
[37]   Calcineurin-independent inhibition of mitochondrial Ca2+ uptake by cyclosporin A [J].
Montero, M ;
Lobatón, CD ;
Gutierrez-Fernández, S ;
Moreno, A ;
Alvarez, J .
BRITISH JOURNAL OF PHARMACOLOGY, 2004, 141 (02) :263-268
[38]   Circularly permuted green fluorescent proteins engineered to sense Ca2+ [J].
Nagai, T ;
Sawano, A ;
Park, ES ;
Miyawaki, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (06) :3197-3202
[39]   Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death [J].
Nakagawa, T ;
Shimizu, S ;
Watanabe, T ;
Yamaguchi, O ;
Otsu, K ;
Yamagata, H ;
Inohara, H ;
Kubo, T ;
Tsujimoto, Y .
NATURE, 2005, 434 (7033) :652-658
[40]   Tetrahydrobiopterin scavenges superoxide in dopaminergic neurons [J].
Nakamura, K ;
Bindokas, VP ;
Kowlessur, D ;
Elas, M ;
Milstein, S ;
Marks, JD ;
Halpern, HJ ;
Kang, UJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (37) :34402-34407