Single protonation of the reduced quinone in respiratory complex I drives four-proton pumping

Complex I is a key proton-pumping enzyme in bacterial and mitochondrial respiratory electron transport chains. Using quantum chemistry and electrostatic calculations, we have examined the pKa of the reduced quinone QH-/QH2 in the catalytic cavity of complex I. We find that pKa (QH-/QH2) is very high, above 20. This means that the energy of a single protonation reaction of the doubly reduced quinone (i.e. the reduced semiquinone QH-) is sufficient to drive four protons across the membrane with a potential of 180 mV. Based on these calculations, we propose a possible scheme of redox-linked proton pumping by complex I. The model explains how the energy of the protonation reaction can be divided equally among four pumping units of the pump, and how a single proton can drive translocation of four additional protons in multiple pumping blocks.

Automated summary

Using quantum chemistry and electrostatic calculations, the pKa of the reduced quinone in the catalytic cavity of complex I is found to be very high, indicating that a single protonation reaction can drive four protons across the membrane. Based on these calculations, a possible scheme of redox-linked proton pumping by complex I is proposed.