Skip to main content
SpringerLink
Log in

Role of Fe(III) in Fe(II)citrate-mediated peroxidation of mitochondrial membrane lipids

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

In this report we study the effect of Fe(III) on lipid peroxidation induced by Fe(II)citrate in mitochondrial membranes, as assessed by the production of thiobarbituric acid-reactive substances and antimycin A-insensitive oxygen uptake. The presence of Fe(III) stimulates initiation of lipid peroxidation when low citrate:Fe(II) ratios are used (≤ 4:1). For a citrate:total iron ratio of 1:1 the maximal stimulation of lipid peroxidation by Fe(III) was observed when the Fe(II):Fe(III) ratio was in the range of 1:1 to 1:2. The lag phase that accompanies oxygen uptake was greatly diminished by increasing concentrations of Fe(III) when the citrate:total iron ratio was 1:1, but not when this ratio was higher. It is concluded that the increase of lipid peroxidation by Fe(III) is observed only when low citrate:Fe(II) ratios were used. Similar results were obtained using ATP as a ligand of iron. Monitoring the rate of spontaneous Fe(II) oxidation by measuring oxygen uptake in buffered medium, in the absence of mitochondria, Fe(III)-stimulated oxygen consumption was observed only when a low citrate:Fe(II) ratio was used. This result suggests that Fe(III) may facilitate the initiation and/or propagation of lipid peroxidation by increasing the rate of Fe(II)citrate-generated reactive oxygen species.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Kappus A: Lipid peroxidation: mechanisms, analysis, enzymology and biological relevance. In: H Sies (ed). Oxidative Stress. Academic Press Inc., London, 1985, pp 273–310

    Google Scholar 

  2. Halliwell B, Chirico S: Lipid peroxidation: Its mechanism, measurement, and significance. Am J Clin Nutr 57: 715S–725S, 1993

    Google Scholar 

  3. Bindoli A: Lipid peroxidation in mitochondria. Free Rad Biol Med 5: 247–261, 1988

    Google Scholar 

  4. Dinis TCP, Almeida LM, Madeira VMC: Lipid peroxidation in sarcoplasmic reticulum membranes: Effect on functional and biophysical properties. Arch Biochem Biophys 301: 256–264, 1993

    Google Scholar 

  5. Castilho RF, Meinicke AR, Almeida AM, Hermes-Lima M, Vercesi AE: Oxidative damage of mitochondria induced by Fe(II)citrate is potentiated by Ca2+ and includes lipid peroxidation and alterations in membrane proteins. Arch Biochem Biophys 308: 158–163, 1994

    Google Scholar 

  6. Castilho RF, Kowaltowski AJ, Meinicke AR, Vercesi AE: Oxidative damage of mitochondria induced by Fe(II)citrate or t-butyl hydroperoxide in the presence of Ca2+: Effect of coenzyme Q redox state. Free Rad Biol Med 18: 55–59, 1995

    Google Scholar 

  7. Formark-Andrée P, Lee C-P, Dallner G, Ernster L: Lipid peroxidation and changes in the ubiquinone content and the respiratory chain enzymes of submitochondrial particles. Free Rad Biol Med 22: 391–400, 1997

    Google Scholar 

  8. Stark G: The effect of ionizing radiation on lipid membranes. Biochim Biophys Acta 1071: 103–122, 1991

    Google Scholar 

  9. Nantes IL, Cilento G, Bechara EJH, Vercesi AE: Chemiluminescent diphenyllacetaldehyde oxidation by mitochondria is promoted by cytochromes and leads to oxidative injury of the organelle. Photochem Photobiol 62: 522–527, 1995

    Google Scholar 

  10. Kowaltowski AJ, Castilho RF, Grijalba MT, Bechara EJH, Vercesi AE: Effect of inorganic phosphate concentration on the nature of inner mitochondrial membrane alterations mediated by Ca2+ ions. A proposed model for phosphate-stimulated lipid peroxidation. J Biol Chem 271: 2929–2934, 1996

    Google Scholar 

  11. Aikens J, Dix TA: Perhydroxyl radical (HO2·) initiated lipid peroxidation. The role of fatty acid hydroperoxides. J Biol Chem 266: 15091–15098, 1991

    Google Scholar 

  12. Gadelha FR, Thomson L, Fagian MM, Costa AD, Radi R, Vercesi AE: Ca2+-independent permeabilization of the inner mitochondrial membrane by peroxynitrite is mediated by membrane protein thiol crosslinking and lipid peroxidation. Arch Biochem Biophys 345: 243–250, 1997

    Google Scholar 

  13. Gutteridge JMC: Ferrous ion-EDTA-stimulated phospholipid peroxidation. A reaction changing from alkoxyl-radical-to hydroxyl-radicaldependent initiation. Biochem J 224: 697–701, 1984

    Google Scholar 

  14. Minotti G, Aust SD: An investigation into the mechanism of citrate-Fe(II)-dependent lipid peroxidation. Free Rad Biol Med 3: 379–387, 1987

    Google Scholar 

  15. Ursini F, Maiorino M, Hochstein P, Ernster L: Microsomal lipid peroxidation: Mechanisms of initiation. The role of iron and iron chelators. Free Rad Biol Med 6: 31–36, 1989

    Google Scholar 

  16. Shivaswamy V, Ramakrishna Kurup CK, Ramasarma T: Ferrous-iron induces lipid peroxidation with little damage to energy transduction in mitochondria. Mol Cell Biochem 120: 141–149, 1993

    Google Scholar 

  17. Carini R, Parola M, Dianzani MU, Albano E: Mitochondrial damage and its role in causing hepatocyte injury during stimulation of lipid peroxidation by iron nitriloacetate. Arch Biochem Biophys 297: 110–118, 1992

    Google Scholar 

  18. Hermes-Lima M, Castilho RF, Meinicke AR, Vercesi AE: Characteristics of Fe(II)ATP complex-induced damage to the rat liver mitochondrial membrane. Mol Cell Biochem 145: 53–60, 1995

    Google Scholar 

  19. Bacon BR, Britton RS: The pathology of hepatic iron overload: A free radical-mediated process? Hepatology 11: 127–137, 1990

    Google Scholar 

  20. Bacon BR, Tavill AS, Britton RS: In: JH Brock, JW Halliday, MJ Pippard, LW Powell (eds). Iron Metabolism in Health and Disease. W.B. Sauders Company Ltd, London, 1994, pp 311–351

    Google Scholar 

  21. Gutteridge JMC: The role of superoxide and hydroxyl radicals in phospholipid peroxidation catalysed by iron salts. FEBS Lett 150: 454–458, 1982

    Google Scholar 

  22. Minotti G, Aust SD: The requirement for iron(III) in the initiation of lipid peroxidation by iron(II) and hydrogen peroxide. J Biol Chem 262: 1098–1104, 1987

    Google Scholar 

  23. Halliwell B, Gutteridge JMC: Role of free radicals and catalytic metal ions in human disease: An overview. Meth Enzymol 186: 1–85, 1990

    Google Scholar 

  24. Hochstein P, Ernster L: ADP-activated lipid peroxidation coupled to the TPNH oxidase system of microsomes. Biochem Biophys Res Commun 12: 388–394, 1963

    Google Scholar 

  25. Sassa H, Takaishi Y, Terada H: The triterpene celastrol as a very potent inhibitor of lipid peroxidation in mitochondria. Biochem Biophys Res Commun 172: 890–897, 1990

    Google Scholar 

  26. Buege JA, Aust SD: Microsomal lipid peroxidation. Meth Enzymol 52: 302–310, 1978

    Google Scholar 

  27. Aruoma OI, Halliwell B, Laughton MJ, Quinlan GJ, Gutteridge JMC: The mechanism of initiation of lipid peroxidation. Evidence against a requirement for an iron(II)-iron(III) complex. Biochem J 258: 617–620, 1989

    Google Scholar 

  28. Tadolini B, Hakim G: The mechanism of iron (III) stimulation of lipid peroxidation. Free Rad Res 25: 221–227, 1996.

    Google Scholar 

  29. Verstraeten SV, Nogueira LV, Schreier S, Oteiza PI: Effect of trivalent metal ions on phase separation and membrane lipid packing: role in lipid peroxidation. Arch Biochem Biophys 338: 121–127, 1997

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departamento de Patologia Clínica, NMCE, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, Brazil

    Roger F. Castilho, André R Meinicke & Anibal E. Vercesi

  2. Oxyradical Research Group, Departamento de Biologia Celular, Universidade de Brasília, Brasília, Brazil

    Marcelo Hermes-Lima

Authors
  1. Roger F. Castilho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. André R Meinicke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anibal E. Vercesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marcelo Hermes-Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Castilho, R.F., Meinicke, A.R., Vercesi, A.E. et al. Role of Fe(III) in Fe(II)citrate-mediated peroxidation of mitochondrial membrane lipids. Mol Cell Biochem 196, 163–168 (1999). https://doi.org/10.1023/A:1006988129221

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006988129221

Search

Navigation