Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/26990
Title: Superoxide constitutes a major signal of mitochondrial superoxide flash
Authors: Zhang, X
Huang, Z
Hou, T
Xu, J
Wang, Y
Shang, W
Ye, T 
Cheng, H
Gao, F
Wang, X
Keywords: Mitochondria
Reactive oxygen species
ROS indicators
Issue Date: 2013
Publisher: Pergamon-Elsevier Science Ltd
Source: Life sciences, 2013, v. 93, no. 4, p. 178-186 How to cite?
Journal: Life Sciences 
Abstract: Aims Mitochondrial flashes detected with an N- and C-terminal circularly-permuted yellow fluorescent protein (cpYFP) have been thought to represent transient and quantal bursts of superoxide production under physiological, stressful and pathophysiological conditions. However, the superoxide nature of the cpYFP-flash has been challenged, considering the pH-sensitivity of cpYFP and the distinctive regulation of the flash versus the basal production of mitochondrial reactive oxygen species (ROS). Thus, the aim of the study is to further determine the origin of mitochondrial flashes. Main methods We investigated the origin of the flashes using the widely-used pH-insensitive ROS indicators, mitoSOX, an indicator for superoxide, and 2, 7-dichlorodihydrofluorescein diacetate (DCF), an indicator for H 2O2 and other oxidants. Key findings Robust, quantal, and stochastic mitochondrial flashes were detected with either mitoSOX or DCF in several cell-types and in mitochondria isolated from the heart. Both mitoSOX-flashes and DCF-flashes showed similar incidence and kinetics to those of cpYFP-flashes, and were equally sensitive to mitochondria-targeted antioxidants. Furthermore, they were markedly decreased by inhibitors or an uncoupler of the mitochondrial electron transport chain, as is the case with cpYFP-flashes. The involvement of the mitochondrial permeability transition pore in DCF-flashes was evidenced by the coincidental loss of mitochondrial membrane potential and matrix-enriched rhod-2, as well as by their sensitivity to cyclosporine A. Significance These data indicate that all the three types of mitochondrial flashes stem from the common physiological process of bursting superoxide and ensuing H2O2 production in the matrix of single mitochondrion.
URI: http://hdl.handle.net/10397/26990
ISSN: 0024-3205
DOI: 10.1016/j.lfs.2013.06.012
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