Energy converting NADH:quinone oxidoreductase (complex I)

Annu Rev Biochem. 2006:75:69-92. doi: 10.1146/annurev.biochem.75.103004.142539.


NADH:quinone oxidoreductase (complex I) pumps protons across the inner membrane of mitochondria or the plasma membrane of many bacteria. Human complex I is involved in numerous pathological conditions and degenerative processes. With 14 central and up to 32 accessory subunits, complex I is among the largest membrane-bound protein assemblies. The peripheral arm of the L-shaped molecule contains flavine mononucleotide and eight or nine iron-sulfur clusters as redox prosthetic groups. Seven of the iron-sulfur clusters form a linear electron transfer chain between flavine and quinone. In most organisms, the seven most hydrophobic subunits forming the core of the membrane arm are encoded by the mitochondrial genome. Most central subunits have evolved from subunits of different hydrogenases and bacterial Na+/H+ antiporters. This evolutionary origin is reflected in three functional modules of complex I. The coupling mechanism of complex I most likely involves semiquinone intermediates that drive proton pumping through redox-linked conformational changes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Electron Transport Complex I* / chemistry
  • Electron Transport Complex I* / genetics
  • Electron Transport Complex I* / metabolism
  • Humans
  • Iron-Sulfur Proteins / chemistry
  • Iron-Sulfur Proteins / genetics
  • Iron-Sulfur Proteins / metabolism
  • Mitochondria / metabolism
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / metabolism
  • Models, Molecular
  • Oxidation-Reduction
  • Protein Conformation
  • Protein Subunits* / chemistry
  • Protein Subunits* / genetics
  • Protein Subunits* / metabolism
  • Protons


  • Iron-Sulfur Proteins
  • Protein Subunits
  • Protons
  • Electron Transport Complex I