Metabolic energy obtained from the coupled chemical reactions of oxidative phosphorylation (OX PHOS) is harnessed in the form of ATP by cells. We experimentally measured thermodynamic forces and fluxes during ATP synthesis, and calculated the thermodynamic efficiency, eta and the rate of free energy dissipation, Phi. We show that the OX PHOS system is tuned such that the coupled nonequilibrium processes operate at optimal eta. This state does not coincide with the state of minimum Phi but is compatible with maximum Phi under the imposed constraints. Conditions that must hold for species concentration in order to satisfy the principle of optimal efficiency are derived analytically and a molecular explanation based on Nath's torsional mechanism of energy transduction and ATP synthesis is suggested. Differences of the proposed principle with Prigogine's principle are discussed. (C) 2018 Elsevier B.V. All rights reserved.