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Respiration-dependent H2O2 Removal in Brain Mitochondria via the Thioredoxin/Peroxiredoxin System
Open accessAbstract
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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“In this context, it is important to note that the H 2 O 2 scavenger activities of isolated mitochondria are lower with succinate as the sole substrate than with NADH-generating substrates like malate/glutamate or malate/pyruvate [111,112].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [112]
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Citations
Cites
How mitochondria produce reactive oxygen species
Murphy, M. P. (2009) · Biochemical Journal · doi:10.1042/bj20081386 · Cited by 8,207
Wendel, A. (1981) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(81)77046-0 · Cited by 3,032
H 2 O 2 , a Necessary Evil for Cell Signaling
Rhee, S. G. (2006) · Science · doi:10.1126/science.1130481 · Cited by 2,160
Oxidative stress in neurodegeneration: Cause or consequence?
Andersen, J. K. (2004) · Nature Medicine · doi:10.1038/nrn1434 · Cited by 1,869
Extension of murine life span by overexpression of catalase targeted to mitochondria
Schriner, S. E., Linford, N. J., Martin, G. M., Treuting, P., Ogburn, C. E., Emond, M., Coskun, P. E., Ladiges, W., Wolf, N., Van Remmen, H., et al. (2005) · Science · doi:10.1126/science.1106653 · Cited by 1,724
Mitochondrial metabolism of reactive oxygen species
Andreyev, A. Y., Kushnareva, Y. E., & Starkov, A. A. (2005) · Biochemistry (Moscow) · doi:10.1007/s10541-005-0102-7 · Cited by 1,336
Generation of reactive oxygen species by the mitochondrial electron transport chain
Liu, Y., Fiskum, G., & Schubert, D. (2002) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2002.00744.x · Cited by 1,260
Glutathione, oxidative stress and neurodegeneration
Schulz, J. B., Lindenau, J. H., Seyfried, J., & DICHGANS, J. (2000) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2000.01595.x · Cited by 1,225
Lebovitz, R. M., Zhang, H., Vogel, H., Cartwright, J., Dionne, L., Lu, N., Huang, S., & Matzuk, M. M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.18.9782 · Cited by 1,023
Environmental risk factors and Parkinson's disease
Liou, H., Tsai, M.-C., Chen, C., Jeng, J., Chang, Y. C., Chen, S. Y., & Chen, R.-T. (1997) · Neurology · doi:10.1212/wnl.48.6.1583 · Cited by 616
Detection of catalase in rat heart mitochondria.
Radi, R., Turrens, J. F., Chang, L. Y., Bush, K. M., Crapo, J. D., & Freeman, B. A. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)54740-2 · Cited by 573
Respiratory chain linked H2O2 production in pigeon heart mitochondria
Loschen, G., & Flohé, L. (1971) · FEBS Letters · doi:10.1016/0014-5793(71)80459-3 · Cited by 552
Mitochondria Are a Major Source of Paraquat-induced Reactive Oxygen Species Production in the Brain
Castello, P. R., Drechsel, D. A., & Patel, M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700827200 · Cited by 477
Self-citationSeo, M. S., Kang, S. W., Kim, K., Baines, I., Lee, T., & Rhee, S. G. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001943200 · Cited by 473
Nonn, L., Williams, R. R., Erickson, R. P., & Powis, G. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.3.916-922.2003 · Cited by 438
Role for mitochondrial oxidants as regulators of cellular metabolism
Nemoto, S., Takeda, K., Yu, Z.-X., Ferrans, V. J., & Finkel, T. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.19.7311-7318.2000 · Cited by 393
The role of mitochondrial oxidative stress in aging
Sastre, J. (2003) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(03)00184-9 · Cited by 346
Preparation and assay of mammalian thioredoxin and thioredoxin reductase
Arnér, E. S. J., Zhong, L., & Holmgren, A. (1999) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(99)00129-9 · Cited by 323
Parkinson's disease: A case‐control study of occupational and environmental risk factors
Hertzman, C., Wiens, M., Bowering, D. J., Snow, B. J., & Calne, D. B. (1990) · American Journal of Industrial Medicine · doi:10.1002/ajim.4700170307 · Cited by 290
Aberrant expression of peroxiredoxin subtypes in neurodegenerative disorders
Krapfenbauer, K., Engidawork, E., Cairns, N. J., Fountoulakis, M., & Lübec, G. (2003) · Brain Research · doi:10.1016/s0006-8993(02)04243-9 · Cited by 288
Isolation of mitochondria from rat brain using Percoll density gradient centrifugation
Sims, N. R., & Anderson, M. F. (2008) · Nature Protocols · doi:10.1038/nprot.2008.105 · Cited by 270
Differential oxidation of thioredoxin-1, thioredoxin-2, and glutathione by metal ions*
Hansen, J. M., Zhang, H., & Jones, D. P. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.09.023 · Cited by 248
Isoforms of mammalian peroxiredoxin that reduce peroxides in presence of thioredoxin
Chae, H. Z., Kang, S. W., & Rhee, S. G. (1999) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(99)00128-7 · Cited by 238
Catalase Takes Part in Rat Liver Mitochondria Oxidative Stress Defense
Salvi, M., Battaglia, V., Brunati, A. M., La Rocca, N., Tibaldi, E., Pietrangeli, P., Marcocci, L., Mondovi, B., Rossi, C. A., & Toninello, A. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m701589200 · Cited by 231
Thioredoxin system inhibitors as mediators of apoptosis for cancer therapy
Tonissen, K. F., & Trapani, G. D. (2008) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200700492 · Cited by 228
Thioredoxin Reductase Activity Is Decreased by Selenium Deficiency
Hill, K. E., McCollum, G. W., Boeglin, M. E., & Burk, R. F. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6618 · Cited by 215
Mitochondrial calcium function and dysfunction in the central nervous system
Nicholls, D. G. (2009) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2009.03.010 · Cited by 213
Hydrogen Peroxide Production by Rat Brain In Vivo
Sinet, P. M., Heikkila, R. E., & Cohen, G. (1980) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1980.tb11222.x · Cited by 197
Hinerfeld, D. A., Traini, M. D., Weinberger, R. P., Cochran, B. C., Doctrow, S. R., Harry, J. L., & Melov, S. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02195.x · Cited by 180
Boveris, A., & Cadenas, E. (2000) · IUBMB Life · doi:10.1080/713803732 · Cited by 171
Kim, S. H., Fountoulakis, M., Cairns, N. J., & Lübec, G. (2001) · Springer eBooks · doi:10.1007/978-3-7091-6262-0_18 · Cited by 138
Respiration-dependent Removal of Exogenous H2O2 in Brain Mitochondria
Zoccarato, F., Cavallini, L., & Alexandre, A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m308143200 · Cited by 130
Boveris, A., & Cadenas, E. (2000) · IUBMB Life · doi:10.1080/15216540051080912 · Cited by 115
Rigobello, M., Folda, A., Baldoin, M. C., Scutari, G., & Bindoli, A. (2005) · Free radical research · doi:10.1080/10715760500135391 · Cited by 103
Absolute Gene Expression Patterns of Thioredoxin and Glutaredoxin Redox Systems in Mouse
Jurado, J., Prieto‐Álamo, M., Madrid-Rísquez, J., & Pueyo, C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307866200 · Cited by 95
Establishing Biomarkers of Oxidative Stress: The Measurement of Hydrogen Peroxide in Human Urine
Halliwell, B. B., Long, L. H., Yee, T. P., Lim, S., & Kelly, R. P. (2004) · Current Medicinal Chemistry · doi:10.2174/0929867043365404 · Cited by 95
Guidot, D. M., Repine, J. E., Kitlowski, A. D., Flores, S. C., Nelson, S. K., Wright, R. M., & McCord, J. M. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118100 · Cited by 82
Mitochondrial peroxiredoxin 3 is rapidly oxidized in cells treated with isothiocyanates
Brown, K., Eriksson, S. E., Arnér, E. S. J., & Hampton, M. B. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.04.030 · Cited by 74
Pk, J. (1966) · Biochimica et Biophysica Acta (BBA) - Enzymology and Biological Oxidation · doi:10.1016/0926-6593(66)90058-0 · Cited by 74
Expression of novel antioxidant thioredoxin‐2 in the rat brain
Rybnikova, E. A., Damdimopoulos, A. E., Gustafsson, J.-Α., Spyrou, G., & Pelto‐Huikko, M. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00059.x · Cited by 72
Reactive oxygen species regulation by AIF- and complex I-depleted brain mitochondria
Chinta, S. J., Rane, A., Yadava, N., Andersen, J. K., Nicholls, D. G., & Polster, B. M. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.01.010 · Cited by 64
Prasad, K. N., Carvalho, É., Kentroti, S., Edwards‐Prasad, J., Freed, C. R., & Vernadakis, A. (1994) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/bf02631258 · Cited by 60
Thioredoxin reductase-1 knock down does not result in thioredoxin-1 oxidation
Watson, W. H., Heilman, J. M., Hughes, L. L., & Spielberger, J. C. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.02.006 · Cited by 54
Calcium-Dependent Oxidation of Thioredoxin during Cellular Growth Initiation
Gitler, C., Zarmi, B., Kalef, E., Meller, R., Zor, U., & Goldman, R. (2002) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.6214 · Cited by 40
Inhibition of Mitochondrial Hydrogen Peroxide Production by Lipophilic Metalloporphyrins
Castello, P. R., Drechsel, D. A., Day, B. J., & Patel, M. (2007) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.132134 · Cited by 40
Self-citationChapter 21 Paraquat‐Induced Production of Reactive Oxygen Species in Brain Mitochondria
Drechsel, D. A., & Patel, M. (2009) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(08)04421-2 · Cited by 39
Self-citationMonitoring Antisense Oligodeoxynucleotide Activity in Hematopoietic Cells
Sokol, D. L., & Gewirtz, A. M. (1999) · Methods · doi:10.1006/meth.1998.0732 · Cited by 35
Research works printed but not linked: 3
- Rogers, 2005, Proc. Am. Assoc. Cancer Res., 46, 454
- Kim, 2001, J. Neural Transm. Suppl., 223
- Andreyev, 2005, Biochemistry, 70, 200
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Tretter, L., Patócs, A., & Chinopoulos, C. (2016) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2016.03.012 · Cited by 550
Molecular Mechanisms of Superoxide Production by the Mitochondrial Respiratory Chain
Dröse, S., & Brandt, U. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-3573-0_6 · Cited by 536
Energy metabolism and inflammation in brain aging and Alzheimer’s disease
Yin, F., Sancheti, H., Patil, I., & Cadenas, E. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.200 · Cited by 538
Superoxide generation by complex III: From mechanistic rationales to functional consequences
Bleier, L., & Dröse, S. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2012.12.002 · Cited by 369
Redox Signaling Mediated by Thioredoxin and Glutathione Systems in the Central Nervous System
Ren, X., Zou, L., Zhang, X., Branco, V., Wang, J., Carvalho, C. M. L., Holmgren, A., & Lu, J. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6925 · Cited by 376
Metadata
- Authors
- Drechsel, D. A., & Patel, M.
- Affiliations
- University of Colorado Denver (US)
- Corresponding author
- Patel, Manisha
- ORCID
- 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)
- PMC
- PMC2934652
- 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
- hybrid
- doi.org
- Licence
- 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 (medical) › 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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