The site of production of superoxide radical in mitochondrial Complex I is not a bound ubisemiquinone but presumably iron-sulfur cluster N2

FEBS Lett. 2001 Sep 21;505(3):364-8. doi: 10.1016/s0014-5793(01)02850-2.


The mitochondrial respiratory chain is a powerful source of reactive oxygen species, considered as the pathogenic agent of many diseases and of aging. We have investigated the role of Complex I in superoxide radical production in bovine heart submitochondrial particles and found, by combined use of specific inhibitors of Complex I and by Coenzyme Q (CoQ) extraction from the particles, that the one-electron donor in the Complex to oxygen is a redox center located prior to the binding sites of three different types of CoQ antagonists, to be identified with a Fe-S cluster, most probably N2 on the basis of several known properties of this cluster. Short chain CoQ analogs enhance superoxide formation, presumably by mediating electron transfer from N2 to oxygen. The clinically used CoQ analog, idebenone, is particularly effective in promoting superoxide formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Coenzymes
  • Electron Transport Complex I
  • Enzyme Inhibitors / pharmacology
  • Hydroxymercuribenzoates / pharmacology
  • Iron-Sulfur Proteins / metabolism*
  • Mitochondria, Heart / drug effects
  • Mitochondria, Heart / enzymology*
  • NADH, NADPH Oxidoreductases / antagonists & inhibitors
  • NADH, NADPH Oxidoreductases / metabolism*
  • Oxidation-Reduction
  • Submitochondrial Particles / drug effects
  • Submitochondrial Particles / enzymology
  • Superoxides / metabolism*
  • Ubiquinone / analogs & derivatives
  • Ubiquinone / metabolism*


  • Coenzymes
  • Enzyme Inhibitors
  • Hydroxymercuribenzoates
  • Iron-Sulfur Proteins
  • Superoxides
  • Ubiquinone
  • 4-hydroxymercuribenzoate
  • NADH, NADPH Oxidoreductases
  • Electron Transport Complex I
  • coenzyme Q10