Abstract
Respiratory mitochondria spontaneously undergo quantal, brief bursts of superoxide production, named “superoxide flashes.” A property common to all species and cell types examined, the generation of superoxide flashes is coupled to transient opening of the mitochondrial membrane permeability transition pore and depends on the functional integrity of the electron-transfer chain (ETC). The unitary properties of superoxide flashes (amplitude and duration) appear to be stereotypical, at levels from isolated mitochondria to whole organs (e.g., the beating heart) and even to live animals. Functionally, superoxide flashes act as elemental reactive oxygen species (ROS) signaling events (“signaling ROS”) that participate in diverse cellular processes, whereas the constitutive electron leakage of molecular oxygen from the ETC produces the bulk of ROS for the regulation of redox homeostasis (“homeostatic ROS”). In particular, superoxide flash incidence provides a digital readout to gauge glucose- and insulin-stimulated mitochondrial metabolism in live animals, and a novel biomarker of the oxidative stress in hyperosmotic stress, ischemia-reperfusion injury, and neurodegenerative diseases. Such dynamic, locally high levels of ROS in the form of superoxide flashes constitute one of the earliest signals that initiate the cell-death program without appreciably affecting the global ROS level. Moreover, in contrast to the effects of global ROS, superoxide flashes negatively regulate neuronal progenitor cell self-renewal in the developing cerebral cortex. Thus, recent advances in “flashology” have bolstered the notion that ROS act as second messengers in physiological and pathophysiological contexts, and demonstrate the paramount importance of the spatiotemporal organization of ROS signals in determining their signaling efficiency and modality.
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Acknowledgments
We thank Iain C. Bruce for critical comments and editing. This work was supported by the National Basic Research Program of China (2013CB531200 and 2011CB809102), the National Science Foundation of China (31221002, 31130067, 31123004 and 30900264) and NIH Grants HL114760 to WW.
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Wang, X., Ma, Q., Wang, W., Cheng, H. (2014). Mitochondrial Superoxide Flashes – From Signaling to Disease. In: Laher, I. (eds) Systems Biology of Free Radicals and Antioxidants. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30018-9_189
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