NDLI: Sites of Superoxide and Hydrogen Peroxide Production by Muscle Mitochondria Assessed ex Vivo under Conditions Mimicking Rest and Exercise

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Sites of Superoxide and Hydrogen Peroxide Production by Muscle Mitochondria Assessed ex Vivo under Conditions Mimicking Rest and Exercise

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Quinlan, Casey L. Goncalves, Renata L. S. Perevoshchikova, Irina V. Hey-mogensen, Martin Brand, Martin D.
Description	Author Affiliation: Goncalves RL ( From the Buck Institute for Research on Aging, Novato, California 94945 rgoncalves@buckinstitute.org.); Quinlan CL ( From the Buck Institute for Research on Aging, Novato, California 94945.); Perevoshchikova IV ( From the Buck Institute for Research on Aging, Novato, California 94945 rgoncalves@buckinstitute.org.); Hey-Mogensen M ( From the Buck Institute for Research on Aging, Novato, California 94945.); Brand MD ( From the Buck Institute for Research on Aging, Novato, California 94945 rgoncalves@buckinstitute.org.)
Abstract	The sites and rates of mitochondrial production of superoxide and H2O2 in vivo are not yet defined. At least 10 different mitochondrial sites can generate these species. Each site has a different maximum capacity (e.g. the outer quinol site in complex III (site IIIQo) has a very high capacity in rat skeletal muscle mitochondria, whereas the flavin site in complex I (site IF) has a very low capacity). The maximum capacities can greatly exceed the actual rates observed in the absence of electron transport chain inhibitors, so maximum capacities are a poor guide to actual rates. Here, we use new approaches to measure the rates at which different mitochondrial sites produce superoxide/H2O2 using isolated muscle mitochondria incubated in media mimicking the cytoplasmic substrate and effector mix of skeletal muscle during rest and exercise. We find that four or five sites dominate during rest in this ex vivo system. Remarkably, the quinol site in complex I (site IQ) and the flavin site in complex II (site IIF) each account for about a quarter of the total measured rate of H2O2 production. Site IF, site IIIQo, and perhaps site EF in the ß-oxidation pathway account for most of the remainder. Under conditions mimicking mild and intense aerobic exercise, total production is much less, and the low capacity site IF dominates. These results give novel insights into which mitochondrial sites may produce superoxide/H2O2 in vivo.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	1
Volume Number	290
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2015-01-02
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Electron Transport Complex I Metabolism Hydrogen Peroxide Mitochondria, Muscle Muscle, Skeletal Superoxides Animals Cytochromes b Electron Transport Complex II Malates Drug Effects Oligomycins Pharmacology Oxygen Consumption Physiology Physical Conditioning, Animal Rats, Wistar Succinic Acid Tissue Culture Techniques Uncoupling Agents Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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