Alternative oxidase present in procyclic Trypanosoma brucei may act to lower the mitochondrial production of superoxide.
The mitochondrial electron transfer chain present in the procyclic form of the African trypanosome Trypanosoma brucei contains both cytochrome c oxidase and an alternative oxidase (TAO) as terminal oxidases that reduce oxygen to water. By contrast, the electron transfer chain of the primitive mitochondrion present in the bloodstream form of T. brucei contains only TAO as the terminal oxidase. TAO functions in the bloodstream forms to oxidize the ubiquinol produced by the glycerol-3-phosphate shuttle that results in the oxidation of the reduced nicotinamide adenine dinucleotide phosphate produced by glycolysis. The function, however, of TAO in the procyclic forms is unknown. In this study, we found that inhibition of TAO by the specific inhibitor salicylhydroxamic acid stimulates the formation of reactive oxygen species (ROS) in trypanosome mitochondria, resulting in mitochondrial alteration and increased oxidation of cellular proteins. Moreover, the activity and protein content of TAO in procyclic trypanosomes were increased when cells were incubated in the presence of hydrogen peroxide or antimycin A, the cytochrome bc1 complex inhibitor, which also results in increased ROS production. We suggest that one function of TAO in procyclic cells may be to prevent ROS production by removing excess reducing equivalents and transferring them to oxygen.
Fang
Jing
J
Department of Biochemistry and Molecular Pharmacology, West Virginia University, School of Medicine, PO Box 9142, Morgantown, WV 26506-9142, USA. jfang@hsc.wvu.edu <jfang@hsc.wvu.edu>
Beattie
Diana S
DS
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D004579:Electron Transport; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015151:Immunoblotting; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010940:Plant Proteins; D017382:Reactive Oxygen Species; D013050:Spectrometry, Fluorescence; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors; D014346:Trypanosoma brucei brucei / Q000201:enzymology*; D000099188:Alternative Oxidase
D000968:Antimycin A; D006861:Hydrogen Peroxide; D024101:Mitochondrial Proteins; D010088:Oxidoreductases; D010100:Oxygen; D010940:Plant Proteins; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D013481:Superoxides; D000099188:Alternative Oxidase