Mitochondrial Targeted Coenzyme Q, Superoxide, and Fuel Selectivity in Endothelial Cells
dc.contributor.author | Fink, Brian D. | |
dc.contributor.author | O'Malley, Yunxia | |
dc.contributor.author | Dake, Brian L. | |
dc.contributor.author | Ross, Nicolette C. | |
dc.contributor.author | Prisinzano, Thomas E. | |
dc.contributor.author | Sivitz, William I. | |
dc.date.accessioned | 2014-03-18T19:43:23Z | |
dc.date.available | 2014-03-18T19:43:23Z | |
dc.date.issued | 2009-01-22 | |
dc.identifier.citation | Fink, B. D., O’Malley, Y., Dake, B. L., Ross, N. C., Prisinzano, T. E., & Sivitz, W. I. (2009). Mitochondrial Targeted Coenzyme Q, Superoxide, and Fuel Selectivity in Endothelial Cells. PLoS ONE, 4(1). http://dx.doi.org/10.1371/journal.pone.0004250 | |
dc.identifier.uri | http://hdl.handle.net/1808/13237 | |
dc.description.abstract | BackgroundPreviously, we reported that the “antioxidant” compound “mitoQ” (mitochondrial-targeted ubiquinol/ubiquinone) actually increased superoxide production by bovine aortic endothelial (BAE) cell mitochondria incubated with complex I but not complex II substrates. Methods and ResultsTo further define the site of action of the targeted coenzyme Q compound, we extended these studies to include different substrate and inhibitor conditions. In addition, we assessed the effects of mitoquinone on mitochondrial respiration, measured respiration and mitochondrial membrane potential in intact cells, and tested the intriguing hypothesis that mitoquinone might impart fuel selectivity in intact BAE cells. In mitochondria respiring on differing concentrations of complex I substrates, mitoquinone and rotenone had interactive effects on ROS consistent with redox cycling at multiple sites within complex I. Mitoquinone increased respiration in isolated mitochondria respiring on complex I but not complex II substrates. Mitoquinone also increased oxygen consumption by intact BAE cells. Moreover, when added to intact cells at 50 to 1000 nM, mitoquinone increased glucose oxidation and reduced fat oxidation, at doses that did not alter membrane potential or induce cell toxicity. Although high dose mitoquinone reduced mitochondrial membrane potential, the positively charged mitochondrial-targeted cation, decyltriphenylphosphonium (mitoquinone without the coenzyme Q moiety), decreased membrane potential more than mitoquinone, but did not alter fuel selectivity. Therefore, non-specific effects of the positive charge were not responsible and the quinone moiety is required for altered nutrient selectivity. ConclusionsIn summary, the interactive effects of mitoquinone and rotenone are consistent with redox cycling at more than one site within complex I. In addition, mitoquinone has substrate dependent effects on mitochondrial respiration, increases repiration by intact cells, and alters fuel selectivity favoring glucose over fatty acid oxidation at the intact cell level. | |
dc.description.sponsorship | This work was supported by Veterans Affairs Medical Research Funds and grant DK25295 from the National Institutes of Health. | |
dc.publisher | Public Library of Science | |
dc.rights | This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. | |
dc.rights.uri | https://creativecommons.org/publicdomain/zero/1.0/ | |
dc.subject | Fuels | |
dc.subject | Glucose | |
dc.subject | Glucose metabolism | |
dc.subject | Membrane potential | |
dc.subject | Mitochondria | |
dc.subject | Oleates | |
dc.subject | Oxidation | |
dc.subject | Oxidation-reduction reactions | |
dc.title | Mitochondrial Targeted Coenzyme Q, Superoxide, and Fuel Selectivity in Endothelial Cells | |
dc.type | Article | |
kusw.kuauthor | Prisinzano, Thomas E. | |
kusw.kudepartment | Medicinal Chemistry | |
kusw.oanotes | PLOS project: This item has a Creative Commons license that allows it to be shared in KU ScholarWorks. | |
kusw.oastatus | fullparticipation | |
dc.identifier.doi | 10.1371/journal.pone.0004250 | |
kusw.oaversion | Scholarly/refereed, publisher version | |
kusw.oapolicy | This item meets KU Open Access policy criteria. | |
dc.rights.accessrights | openAccess |
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