Cited by 67Mitochondrial Function and PathologyCoenzyme Q10 studies and effectsRedox biology and oxidative stress

Succinate modulation of H2O2 release at NADH:ubiquinone oxidoreductase (complex I) in brain mitochondria

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Zoccarato, Franco, Cavallini, Lucia, Bortolami, Silvia, Alexandre, Adolfo·2007·Biochemical Journal

Abstract

Complex I (NADH:ubiquinone oxidoreductase) is responsible for most of the mitochondrial H2O2 release, both during the oxidation of NAD-linked substrates and during succinate oxidation. The much faster succinate-dependent H2O2 production is ascribed to Complex I, being rotenone-sensitive. In the present paper, we report high-affinity succinate-supported H2O2 generation in the absence as well as in the presence of GM (glutamate/malate) (1 or 2 mM of each). In brain mitochondria, their only effect was to increase from 0.35 to 0.5 or to 0.65 mM the succinate concentration evoking the semi-maximal H2O2 release. GM are still oxidized in the presence of succinate, as indicated by the oxygen-consumption rates, which are intermediate between those of GM and of succinate alone when all substrates are present together. This effect is removed by rotenone, showing that it is not due to inhibition of succinate influx. Moreover, α-oxoglutarate production from GM, a measure of the activity of Complex I, is decreased, but not stopped, by succinate. It is concluded that succinate-induced H2O2 production occurs under conditions of regular downward electron flow in Complex I. Succinate concentration appears to modulate the rate of H2O2 release, probably by controlling the hydroquinone/quinone ratio.

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Authors
Zoccarato, F., Cavallini, L., Bortolami, S., & Alexandre, A.
Affiliations
University of Padua (IT)
Venue
Biochemical Journal
Published
2007-07-26
Volume
406
Issue
1
Pages
125-129
ISSN
  • 0264-6021 (ISSN-L)
  • 1470-8728
OpenAlex
W2044707953
Cited by
66
References
26
Citations by year
2025: 2 · 2022: 1 · 2021: 6 · 2020: 2 · 2018: 2 · 2017: 1 · 2016: 4 · 2015: 3 · 2014: 3 · 2013: 7 · 2012: 7
FWCI
2.51
Type
journal article
Language
en
Open access
Locations
  • Biochemical Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion, other-oa)
  • Padua Research Archive (University of Padova) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
succinic acid, hydrogen peroxide release, complex I, brain mitochondria, glutamate-malate, rotenone sensitivity, alpha-oxoglutarate, electron flow, oxygen consumption, NAD-linked substrates
MeSH terms
Animals, Electron Transport, Hydrogen Peroxide, Hydrogen-Ion Concentration, Ketoglutaric Acids, Malates, Mitochondria, Oxidation-Reduction, Oxygen Consumption, Substrate Specificity, Succinates, Titrimetry, Glutamic Acid, Electron Transport Complex I, Rats

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