Long chain fatty acyl-CoA modulation of H2O2 release at mitochondrial complex I
Abstract
Complex I is responsible for most of the mitochondrial H(2)O(2) release, low during the oxidation of the NAD linked substrates and high during succinate oxidation, via reverse electron flow. This H(2)O(2) production appear physiological since it occurs at submillimolar concentrations of succinate also in the presence of NAD substrates in heart (present work) and rat brain mitochondria (Zoccarato et al., Biochem J, 406:125-129, 2007). Long chain fatty acyl-CoAs, but not fatty acids, act as strong inhibitors of succinate dependent H(2)O(2) release. The inhibitory effect of acyl-CoAs is independent of their oxidation, being relieved by carnitine and unaffected or potentiated by malonyl-CoA. The inhibition appears to depend on the unbound form since the acyl-CoA effect decreases at BSA concentrations higher than 2 mg/ml; it is not dependent on DeltapH or Deltap and could depend on the inhibition of reverse electron transfer at complex I, since palmitoyl-CoA inhibits the succinate dependent NAD(P) or acetoacetate reduction.
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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 [108]
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Self-citation
- Authors
- Bortolami, S., Comelato, E., Zoccarato, F., Alexandre, A., & Cavallini, L.
- Affiliations
- University of Padua (IT)
- Corresponding author
- Cavallini, Lucia
- Venue
- Journal of Bioenergetics and Biomembranes
- Published
- 2008-01-24
- Volume
- 40
- Issue
- 1
- Pages
- 9-18
- ISSN
- 0145-479X (ISSN-L)
- 1573-6881
- OpenAlex
- W1992123175
- Cited by
- 13
- References
- 40
- Citations by year
- 2016: 1 · 2014: 1 · 2013: 1
- FWCI
- 1.37
- 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 › Coenzyme Q10 studies and effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- long-chain fatty acyl-CoA, mitochondrial complex I, hydrogen peroxide release, succinate oxidation, reverse electron transfer, NAD-linked substrates, palmitoyl-CoA, L-carnitine, malonyl-CoA, heart mitochondria
- MeSH terms
- Animals, Carnitine, Electron Transport, Hydrogen Peroxide, Malonyl Coenzyme A, Mitochondria, Heart, NADP, Oxidation-Reduction, Succinic Acid, Electron Transport Complex I, Rats
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