Respiratory complex I: A dual relation with H+ and Na+?

Paulo J. Castro, Andreia F. Silva, Bruno C. Marreiros, Ana P. Batista, Manuela Alexandra Pereira

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17 Citations (Scopus)


Respiratory complex I couples NADH:quinone oxidoreduction to ion translocation across the membrane, contributing to the buildup of the transmembrane difference of electrochemical potential. H+ is well recognized to be the coupling ion of this system but some studies suggested that this role could be also performed by Na+. We have previously observed NADH-driven Na+ transport opposite to H+ translocation by menaquinone-reducing complexes I, which indicated a Na+/H+ antiporter activity in these systems. Such activity was also observed for the ubiquinone-reducing mitochondrial complex I in its deactive form. The relation of Na+ with complex I may not be surprising since the enzyme has three subunits structurally homologous to bona fide Na+/H+ antiporters and translocation of H+ and Na+ ions has been described for members of most types of ion pumps and transporters. Moreover, no clearly distinguishable motifs for the binding of H+ or Na+ have been recognized yet. We noticed that in menaquinone-reducing complexes I, less energy is available for ion translocation, compared to ubiquinone-reducing complexes I. Therefore, we hypothesized that menaquinone-reducing complexes I perform Na+/H+ antiporter activity in order to achieve the stoichiometry of 4H+/2e-. In agreement, the organisms that use ubiquinone, a high potential quinone, would have kept such Na+/H+ antiporter activity, only operative under determined conditions. This would imply a physiological role(s) of complex I besides a simple "coupling" of a redox reaction and ion transport, which could account for the sophistication of this enzyme. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt.

Original languageEnglish
Pages (from-to)928-937
Number of pages10
JournalBiochimica et Biophysica Acta-Bioenergetics
Issue number7
Publication statusPublished - 1 Jul 2016


  • Bacteria
  • Evolution
  • NADH:quinone oxidoreductase
  • Respiratory chain
  • Transport


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