Succinate is the controller of O 2 − /H2O2 release at mitochondrial complex I : negative modulation by malate, positive by cyanide
Abstract
Mitochondrial production of H(2)O(2) is low with NAD substrates (glutamate/pyruvate, 3 and 2 mM) (G/P) and increases over ten times upon further addition of succinate, with the formation of a sigmoidal curve (semimaximal value at 290 microM, maximal H(2)O(2) production at 600 microM succinate). Malate counteracts rapidly the succinate induced increased H(2)O(2) release and moves the succinate dependent H(2)O(2) production curve to the right. Nitric oxide (NO) and carbon monoxide (CO) are cytochrome c oxidase inhibitors which increase mitochondrial ROS production. Cyanide (CN(-)) was used to mimic NO and CO. In the presence of G/P and succinate (300 microM), CN(-) progressively increased the H(2)O(2) release rate, starting at 1.5 microM. The succinate dependent H(2)O(2) production curve was moved to the left by 30 microM CN(-). The V(max) was little modified. We conclude that succinate is the controller of mitochondrial H(2)O(2) production, modulated by malate and CN(-). We propose that succinate promotes an interaction between Complex II and Complex I, which activates O(2)(-) production.
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Under specific conditions with pyruvate and glutamate, supplementation with only 15-150 micromolar succinate is enough to significantly increase ROS release from isolated mitochondria.
“Under some specific conditions (i.e. in presence of pyruvate and glutamate), a supplementation of only 15-150 μM succinate is enough to increase ROS release from isolated mitochondria significantly [34].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [34]
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 [34]
The prevalent view is that under these conditions ROS are produced by complex I due to reverse electron transfer from complex II, although alternative explanations have been proposed.
“While alternative explanations for the source or mechanism of ROS production under these conditions have been proposed [34,36], the prevalent view is that under these conditions ROS are produced by complex I due to RET from complex II [18][19][20]23].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [34]
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Reilly, B. (2015) · The University of Queensland · doi:10.14264/uql.2015.587
- Authors
- Zoccarato, F., Cavallini, L., & Alexandre, A.
- Affiliations
- University of Padua (IT)
- Corresponding author
- Alexandre, Adolfo
- Venue
- Journal of Bioenergetics and Biomembranes
- Published
- 2009-08
- Volume
- 41
- Issue
- 4
- Pages
- 387-393
- ISSN
- 0145-479X (ISSN-L)
- 1573-6881
- OpenAlex
- W2471095462
- Cited by
- 31
- References
- 37
- Citations by year
- 2026: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 1 · 2017: 2 · 2016: 2 · 2015: 2 · 2013: 6 · 2012: 5
- FWCI
- 1.61
- 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, mitochondrial complex I, superoxide production, hydrogen peroxide release, malate, cyanide, nitric oxide, carbon monoxide, cytochrome c oxidase inhibition, mitochondrial reactive oxygen species
- MeSH terms
- Animals, Cells, Cultured, Cyanides, Dose-Response Relationship, Drug, Hydrogen Peroxide, Malates, Mitochondria, Superoxides, Reactive Oxygen Species, Succinic Acid, Electron Transport Complex I, Rats
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