Journal of Bioenergetics and Biomembranes

, Volume 32, Issue 6, pp 609–615

Localization of the Site of Oxygen Radical Generation inside the Complex I of Heart and Nonsynaptic Brain Mammalian Mitochondria

  • A. Herrero
  • G. Barja

DOI: 10.1023/A:1005626712319

Cite this article as:
Herrero, A. & Barja, G. J Bioenerg Biomembr (2000) 32: 609. doi:10.1023/A:1005626712319


Mitochondrial production of oxygen radicals seems to be involved in many diseases and aging. Recent studies clearly showed that a substantial part of the free radical generation of rodent mitochondria comes from complex I. It is thus important to further localize the free radical generator site within this respiratory complex. In this study, superoxide production by heart and nonsynaptic brain submitochondrial particles from up to seven mammalian species, showing different longevities, were studied under different conditions. The results, taking together, show that rotenone stimulates NADH-supported superoxide generation, confirming that complex I is a source of oxygen radicals in mammals, in general. The rotenone-stimulated NADH-supported superoxide production of the heart and nonsynaptic brain mammalian submitochondrial particles was inhibited both by p-chloromercuribenzoate and by ethoxyformic anhydride. These results localize the complex I oxygen radical generator between the ferricyanide and the ubiquinone reduction site, making iron—sulfur centers possible candidates, although unstable semiquinones can not be discarded. The results also indicate that the previously described inverse correlation between rates of mitochondrial oxygen radical generation and mammalian longevity operates through mechanisms dependent on the presence of intact functional mitochondria.

Mitochondria free radicals complex I superoxide iron—sulfur centers submitochondrial particles 

Copyright information

© Plenum Publishing Corporation 2000

Authors and Affiliations

  • A. Herrero
    • 1
  • G. Barja
    • 1
  1. 1.Department of Animal Biology-II (Animal Physiology), Faculty of BiologyComplutense UniversityMadridSpain

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