Ubiquinone binding pocket of mitochondrial electron transport chain complex I and complex II

The ubiquinone binding pocket of mitochondrial electron transport chain complex I (NADH:ubiquinone oxidoreductase) and complex II (succinate dehydrogenase) is a highly conserved, substrate-specific site within each multi-subunit enzyme complex. In complex I, this pocket is located in the peripheral arm and forms a tunnel-like structure lined with both hydrophobic and charged residues, facilitating the acceptance of electrons from NADH (by way of multiple iron–sulfur clusters) and the reduction of ubiquinone (coenzyme Q) to ubiquinol. The process is coupled to proton translocation across the inner mitochondrial membrane, which drives ATP synthesis through oxidative phosphorylation[1][2][3][4][6][7]. In complex II, the ubiquinone binding pocket links the tricarboxylic acid cycle to the electron transport chain by accepting electrons from succinate via FAD and several iron–sulfur clusters, transferring them to ubiquinone, and contributing to electron flow into the respiratory chain[5]. Both sites are essential for cellular energy metabolism, and dysfunction at these sites is central to a range of diseases, including neurodegenerative disorders, metabolic diseases, cancer, and ischemia-reperfusion injury; they are also established targets for several classes of inhibitors and study drugs.

Other names

Ubiquinone binding site of complex I and IIQ binding site of mitochondrial complex I and IIQuinone binding pocket of NADH:ubiquinone oxidoreductase and succinate dehydrogenase

Competitive inhibition of ubiquinone binding (prevents electron transfer and redox cycling)[2][7]; Disruption of proton translocation/energy coupling[2]; Inhibition of substrate reduction and ATP synthesis