Cited by 8Mitochondrial Function and PathologyRedox biology and oxidative stressCancer and biochemical research

The control of mitochondrial succinate-dependent H2O2 production

Zoccarato, Franco, Miotto, Claudio, Cavallini, Lucia, Alexandre, Adolfo·2011·Journal of Bioenergetics and Biomembranes

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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Crossref · 10.1007/s10863-011-9363-6

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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
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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