The control of mitochondrial succinate-dependent H2O2 production
Abstract
In brain mitochondria succinate activates H(2)O(2) release, concentration dependently (starting at 15 μM), and in the presence of NAD dependent substrates (glutamate, pyruvate, β-hydroxybutyrate). We report that TCA cycle metabolites (citrate, isocitrate, α-ketoglutarate, fumarate, malate) individually and quickly inhibit H(2)O(2) release. When they are present together at physiological concentration (0.2, 0.01, 0.15, 0.12, 0.2 mM respectively) they decrease H(2)O(2) production by over 60% at 0.1-0.2 mM succinate. The degree of inhibition depends on the concentration of each metabolite. Acetoacetate is a strong inhibitor of H(2)O(2) release, starting at 10 μM and acting quickly. It potentiates the inhibition induced by TCA cycle metabolites. The action of acetoacetate is partially removed by β-hydroxybutyrate. Removal is minimal at 0.1 mM acetoacetate, and is higher at 0.5 mM acetoacetate. We conclude that several inhibitors of H(2)O(2) release act jointly and concentration dependently to rapidly set the required level of H(2)O(2) generation at each succinate concentration.
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Different NADH-generating substrates have opposing effects on ROS generation.
“other studies demonstrated that different NADH-generating substrates have an opposing effect on ROS generation [23,35,108]”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [35]
A high rate of ROS production is observed when NADH-generating substrates and succinate are supplied together to isolated mitochondria.
“A high rate of ROS production is also observed when NADH-generating substrates and succinate are concomitantly supplied to isolated mitochondria [21,23,34,35].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [35]
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- Authors
- Zoccarato, F., Miotto, C., Cavallini, L., & Alexandre, A.
- Affiliations
- University of Padua (IT)
- Corresponding author
- Alexandre, Adolfo
- Venue
- Journal of Bioenergetics and Biomembranes
- Published
- 2011-07-07
- Volume
- 43
- Issue
- 4
- Pages
- 359-366
- ISSN
- 0145-479X (ISSN-L)
- 1573-6881
- OpenAlex
- W2013444476
- Cited by
- 8
- References
- 43
- Citations by year
- 2024: 1 · 2021: 1 · 2020: 1 · 2018: 1 · 2017: 1 · 2013: 2 · 2012: 1
- FWCI
- 0.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Bioenergetics and Biomembranes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- succinic acid, TCA cycle metabolites, acetoacetate, beta-hydroxybutyrate, citrate, isocitrate, alpha-ketoglutarate, fumarate, malate, brain mitochondria, glutamate, pyruvate, reactive oxygen species regulation
- MeSH terms
- Acetoacetates, Animals, Brain, Citric Acid Cycle, Hydrogen Peroxide, Mitochondria, Rats, Wistar, Succinic Acid, Mice, Rats
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