Cited by 200Redox biology and oxidative stressMitochondrial Function and PathologyAntioxidant Activity and Oxidative Stress

Respiration-dependent H2O2 removal in brain mitochondria via the thioredoxin/peroxiredoxin system

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Drechsel, Derek A., Patel, Manisha·2010·Journal of Biological Chemistry

Abstract

Mitochondrial reactive oxygen species (ROS) play an important role in both physiological cell signaling processes and numerous pathological states, including neurodegenerative disorders such as Parkinson disease. While mitochondria are considered the major cellular source of ROS, their role in ROS removal remains largely unknown. Using polarographic methods for real-time detection of steady-state H(2)O(2) levels, we were able to quantitatively measure the contributions of potential systems toward H(2)O(2) removal by brain mitochondria. Isolated rat brain mitochondria showed significant rates of exogenous H(2)O(2) removal (9-12 nmol/min/mg of protein) in the presence of substrates, indicating a respiration-dependent process. Glutathione systems showed only minimal contributions: 25% decrease with glutathione reductase inhibition and no effect by glutathione peroxidase inhibition. In contrast, inhibitors of thioredoxin reductase, including auranofin and 1-chloro-2,4-dinitrobenzene, attenuated H(2)O(2) removal rates in mitochondria by 80%. Furthermore, a 50% decrease in H(2)O(2) removal was observed following oxidation of peroxiredoxin. Differential oxidation of glutathione or thioredoxin proteins by copper (II) or arsenite, respectively, provided further support for the thioredoxin/peroxiredoxin system as the major contributor to mitochondrial H(2)O(2) removal. Inhibition of the thioredoxin system exacerbated mitochondrial H(2)O(2) production by the redox cycling agent, paraquat. Additionally, decreases in H(2)O(2) removal were observed in intact dopaminergic neurons with thioredoxin reductase inhibition, implicating this mechanism in whole cell systems. Therefore, in addition to their recognized role in ROS production, mitochondria also remove ROS. These findings implicate respiration- and thioredoxin-dependent ROS removal as a potentially important mitochondrial function that may contribute to physiological and pathological processes in the brain.

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  1. Lebovitz, R. M., Zhang, H., Vogel, H., Cartwright, J., Jr., Dionne, L., Lu, N., Huang, S., and Matzuk, M. M. (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 9782-9787
  2. Rogers, K. E., and Powis, G. (2005) Proc. Am. Assoc. Cancer Res. 46, 454

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Authors
Drechsel, D. A., & Patel, M.
Affiliations
University of Colorado Denver (US)
Corresponding author
Patel, Manisha
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2010-09
Volume
285
Issue
36
Pages
27850-27858
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2090005130
Cited by
199
References
46
Citations by year
2026: 7 · 2025: 9 · 2024: 6 · 2023: 3 · 2022: 10 · 2021: 13 · 2020: 11 · 2019: 9 · 2018: 13 · 2017: 15 · 2016: 10 · 2015: 20 · 2014: 18 · 2013: 17 · 2012: 20
FWCI
7.16
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Foundation for Pharmaceutical Education
  • National Institutes of Health (RO1NS04748, 1f31ns061438-01a1, RO1NS039587)
  • National Institute of Neurological Disorders and Stroke (1F31NS061438, R01NS039587, R01NS045748, R01NS04748, F31 NS061438, RO1NS039587)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
hydrogen peroxide removal, brain mitochondria, thioredoxin system, peroxiredoxin, thioredoxin reductase, mitochondrial reactive oxygen species, oxidative stress, Parkinson's disease, dopaminergic neurons, glutathione, paraquat, auranofin, arsenite, mitochondrial respiration
MeSH terms
Animals, Brain, Cell Line, Cell Membrane Permeability, Dopamine, Enzyme Inhibitors, Hydrogen Peroxide, Liver, Male, Metals, Mitochondria, Polarography, Thioredoxins, Thioredoxin-Disulfide Reductase, Rats, Sprague-Dawley, Cell Respiration, Rats, Peroxiredoxins

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