Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/31350
Title: Synergistic triggering of superoxide flashes by mitochondrial Ca2+ uniport and basal reactive oxygen species elevation
Authors: Hou, T
Zhang, X
Xu, J
Jian, C
Huang, Z
Ye, T 
Hu, K
Zheng, M
Gao, F
Wang, X
Cheng, H
Issue Date: 2013
Publisher: Amer Soc Biochemistry Molecular Biology Inc
Source: Journal of biological chemistry, 2013, v. 288, no. 7, p. 4602-4612 How to cite?
Journal: Journal of Biological Chemistry 
Abstract: Mitochondrial superoxide flashes reflect a quantal, bursting mode of reactive oxygen species (ROS) production that arises from stochastic, transient opening of the mitochondrial permeability transition pore (mPTP) in many types of cells and in living animals. However, the regulatory mechanisms and the exact nature of the flash-coupled mPTP remain poorly understood. Here we demonstrate a profound synergistic effect between mitochondrial Ca2+ uniport and elevated basal ROS production in triggering superoxide flashes in intact cells. Hyperosmotic stress potently augmented the flash activity while simultaneously elevating mitochondrial Ca2+ and ROS. Blocking mitochondrial Ca2+ transport by knockdown of MICU1 or MCU, newly identified components of the mitochondrial Ca2+ uniporter, or scavenging mitochondrial basal ROS markedly diminished the flash response. More importantly, whereas elevating Ca2+ or ROS production alone was inefficacious in triggering the flashes, concurrent physiological Ca2+ and ROS elevation served as the most powerful flash activator, increasing the flash incidence by an order of magnitude. Functionally, superoxide flashes in response to hyperosmotic stress participated in the activation of JNK and p38. Thus, physiological levels of mitochondrial Ca2+ and ROS synergistically regulate stochastic mPTP opening and quantal ROS production in intact cells, marking the flash as a coincidence detector of mitochondrial Ca2+ and ROS signals.
URI: http://hdl.handle.net/10397/31350
ISSN: 0021-9258
DOI: 10.1074/jbc.M112.398297
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