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

FEBS Lett. 2023 Jan;597(2):237-245. doi: 10.1002/1873-3468.14518. Epub 2022 Nov 2.

Abstract

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.

Keywords: Mitochondria; NADH dehydrogenase; coupled electron-proton transfer; proton pumping; proton translocation; respiratory complex I.

MeSH terms

  • Electron Transport
  • Electron Transport Complex I* / metabolism
  • Oxidation-Reduction
  • Protons*
  • Quinones

Substances

  • Electron Transport Complex I
  • Protons
  • Quinones
  • quinone