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Journal of Bioenergetics and Biomembranes

, Volume 40, Issue 6, pp 587–598 | Cite as

Mitochondrial generation of reactive oxygen species is enhanced at the Qo site of the complex III in the myocardium of Trypanosoma cruzi-infected mice: beneficial effects of an antioxidant

  • Jian-Jun Wen
  • Nisha Jain GargEmail author
Article

Abstract

In this study, we have characterized the cellular source and mechanism for the enhanced generation of reactive oxygen species (ROS) in the myocardium during Trypanosoma cruzi infection. Cardiac mitochondria of infected mice, as compared to normal controls, exhibited 63.3% and 30.8% increase in ROS-specific fluorescence of dihydroethidium (detects O2 •−) and amplex red (detects H2O2), respectively. This increase in ROS level in cardiac mitochondria of infected mice was associated with a 59% and 114% increase in the rate of glutamate/malate- (complex I substrates) and succinate- (complex II substrate) supported ROS release, respectively, and up to a 74.9% increase in the rate of electron leakage from the respiratory chain when compared to normal controls. Inhibition studies with normal cardiac mitochondria showed that rotenone induced ROS generation at the QNf-ubisemiquinone site in complex I. In complex III, myxothiazol induced ROS generation from a site located at the Qo center that was different from the Qi center of O2 •− generation by antimycin. In cardiac mitochondria of infected mice, the rate of electron leakage at complex I during forward (complex I-to-complex III) and reverse (complex II-to-complex I) electron flow was not enhanced, and complex I was not the main site of increased ROS production in infected myocardium. Instead, defects of complex III proximal to the Qo site resulted in enhanced electron leakage and ROS formation in cardiac mitochondria of infected mice. Treatment of infected mice with phenyl-α-tert-butyl-nitrone (PBN) improved the respiratory chain function, and, subsequently, decreased the extent of electron leakage and ROS release. In conclusion, we show that impairment of the Qo site of complex III resulted in increased electron leakage and O2 •− formation in infected myocardium, and was controlled by PBN.

Keywords

Chagas disease Mitochondria Myocardium Reactive oxygen species Electron transport chain Site of ROS production 

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Departments of Microbiology and ImmunologyUniversity of Texas Medical BranchGalvestonUSA
  2. 2.Department of PathologyUniversity of Texas Medical BranchGalvestonUSA
  3. 3.Member of the Institute for Human Infections and Immunity and Sealy Center for Vaccine DevelopmentUniversity of Texas Medical BranchGalvestonUSA
  4. 4.3.142C Medical Research BuildingUniversity of Texas Medical BranchGalvestonUSA

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