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
[1]   Oxidative stress in neurodegeneration: cause or consequence? [J].
Andersen, JK .
NATURE MEDICINE, 2004, 10 (07) :S18-S25
[2]   Synchronized whole cell oscillations in mitochondrial metabolism triggered by a local release of reactive oxygen species in cardiac myocytes [J].
Aon, MA ;
Cortassa, S ;
Marbán, E ;
O'Rourke, B .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (45) :44735-44744
[3]   Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death [J].
Baines, CP ;
Kaiser, RA ;
Purcell, NH ;
Blair, NS ;
Osinska, H ;
Hambleton, MA ;
Brunskill, EW ;
Sayen, MR ;
Gottlieb, RA ;
Dorn, GW ;
Robbins, J ;
Molkentin, JD .
NATURE, 2005, 434 (7033) :658-662
[4]   Titrating the effects of mitochondrial complex I impairment in the cell physiology [J].
Barrientos, A ;
Moraes, CT .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (23) :16188-16197
[5]   Properties of the permeability transition pore in mitochondria devoid of cyclophilin D [J].
Basso, E ;
Fante, L ;
Fowlkes, J ;
Petronilli, V ;
Forte, MA ;
Bernardi, P .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (19) :18558-18561
[6]   Opening of the mitochondrial permeability transition pore induces reactive oxygen species production at the level of the respiratory chain complex I [J].
Batandier, C ;
Leverve, X ;
Fontaine, E .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (17) :17197-17204
[7]   The free radical theory of aging matures [J].
Beckman, KB ;
Ames, BN .
PHYSIOLOGICAL REVIEWS, 1998, 78 (02) :547-581
[8]   Genetically encoded fluorescent indicator for intracellular hydrogen peroxide [J].
Belousov, VV ;
Fradkov, AF ;
Lukyanov, KA ;
Staroverov, DB ;
Shakhbazov, KS ;
Terskikh, AV ;
Lukyanov, S .
NATURE METHODS, 2006, 3 (04) :281-286
[9]   The permeability transition pore. Control points of a cyclosporin A-sensitive mitochondrial channel involved in cell death [J].
Bernardi, P .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 1996, 1275 (1-2) :5-9
[10]   Mitochondrial transport of cations: Channels, exchangers, and permeability transition [J].
Bernardi, P .
PHYSIOLOGICAL REVIEWS, 1999, 79 (04) :1127-1155