On the mechanism of respiratory complex I

The energy-converting NADH:ubiquinone oxidoreductase, respiratory complex I, couples the transfer of electrons from NADH to ubiquinone with the translocation of protons across the membrane. Electron microscopy and X-ray crystallography revealed the two-part structure of the enzyme complex. A peripheral arm extending into the aqueous phase catalyzes the electron transfer reaction. Accordingly, this arm contains the redox-active cofactors, namely one flavin mononucleotide (FMN) and up to ten iron-sulfur (Fe/S) clusters. A membrane arm embedded in the lipid bilayer catalyzes proton translocation by a yet unknown mechanism. The binding site of the substrate (ubi) quinone is located at the interface of the two arms. The oxidation of one NADH is coupled with the translocation of four protons across the membrane. In this review, the binding of the substrates, the intramolecular electron transfer, the role of individual Fe/S clusters and the mechanism of proton translocation are discussed in the light of recent data obtained from our laboratory.