Send to:

Choose Destination
See comment in PubMed Commons below
J Bioenerg Biomembr. 2008 Oct;40(5):475-83. doi: 10.1007/s10863-008-9171-9. Epub 2008 Nov 4.

Challenges in elucidating structure and mechanism of proton pumping NADH:ubiquinone oxidoreductase (complex I).

Author information

  • 1Fachbereich Medizin, Molekulare Bioenergetik, Cluster of Excellence Frankfurt, Macromolecular Complexes, ZBC, Goethe-Universität, Frankfurt am Main, Germany.


Proton pumping NADH:ubiquinone oxidoreductase (complex I) is the most complicated and least understood enzyme of the respiratory chain. All redox prosthetic groups reside in the peripheral arm of the L-shaped structure. The NADH oxidation domain harbouring the FMN cofactor is connected via a chain of iron-sulfur clusters to the ubiquinone reduction site that is located in a large pocket formed by the PSST- and 49-kDa subunits of complex I. An access path for ubiquinone and different partially overlapping inhibitor binding regions were defined within this pocket by site directed mutagenesis. A combination of biochemical and single particle analysis studies suggests that the ubiquinone reduction site is located well above the membrane domain. Therefore, direct coupling mechanisms seem unlikely and the redox energy must be converted into a conformational change that drives proton pumping across the membrane arm. It is not known which of the subunits and how many are involved in proton translocation. Complex I is a major source of reactive oxygen species (ROS) that are predominantly formed by electron transfer from FMNH(2). Mitochondrial complex I can cycle between active and deactive forms that can be distinguished by the reactivity towards divalent cations and thiol-reactive agents. The physiological role of this phenomenon is yet unclear but it could contribute to the regulation of complex I activity in-vivo.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Springer
    Loading ...
    Write to the Help Desk