The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Mitochondrial Aconitase Is a Source of Hydroxyl Radical
Open accessAbstract
Mitochondrial aconitase (m-aconitase) contains a [4Fe-4S](2+) cluster in its active site that catalyzes the stereospecific dehydration-rehydration of citrate to isocitrate in the Krebs cycle. It has been proposed that the [4Fe-4S](2+) aconitase is oxidized by superoxide, generating the inactive [3Fe-4S](1+) aconitase. In this reaction, the likely products are iron(II) and hydrogen peroxide. Consequently, the inactivation of m-aconitase by superoxide may increase the formation of hydroxyl radical ((*)OH) through the Fenton reaction in mitochondria. In this work, evidence for the generation of (*)OH from the reaction of m-aconitase with superoxide is provided using ESR spin trapping experiments with 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide and alpha-phenyl-N-tert-butylnitrone. Formation of free ( small middle dot)OH was verified with the (*)OH scavenger Me(2)SO, which forms methyl radical upon reacting with (*)OH. The addition of Me(2)SO to incubation mixtures containing m-aconitase and xanthine/xanthine oxidase yielded methyl radical, which was detected by ESR spin trapping. Methyl radical formation was further confirmed using [(13)C]Me(2)SO. Parallel low temperature ESR experiments demonstrated that the generation of the [3Fe-4S](1+) cluster increased with increasing additions of superoxide to m-aconitase. This reaction was reversible, as >90% of the initial aconitase activity was recovered upon treatment with glutathione and iron(II). This mechanism presents a scenario in which (*)OH may be continuously generated in the mitochondria.
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Cites
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Cited by
Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release
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Mitochondrial metabolism of reactive oxygen species
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Targeting Antioxidants to Mitochondria by Conjugation to Lipophilic Cations
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Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine
Radi, R. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1804932115 · Cited by 1,142
ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells
Snezhkina, A. V., Kudryavtseva, A. V., Kardymon, O. L., Savvateeva, M. V., Melnikova, N. V., Krasnov, G. S., & Dmitriev, A. A. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/6175804 · Cited by 934
Metadata
- Authors
- Vásquez-Vivar, J., Kalyanaraman, B., & Kennedy, M. C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-05
- Volume
- 275
- Issue
- 19
- Pages
- 14064-14069
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2050945967
- Cited by
- 317
- References
- 31
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
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