Energy-converting respiratory Complex I: On the way to the molecular mechanism of the proton pump

► Respiratory Complex I (CI, NADH:ubiquinone oxidoreductase) remains the most enigmatic of the known H+ pumps. ► Recent X-ray crystal structures and massive mutagenesis have boosted progress in revealing the molecular mechanism of CI. ► The energy-conversion step coupling electron transfer to proton translocation in CI has been identified, although the nature of coupling itself remains unknown. ► Mechanical piston transmission proposed as the coupling principle is discussed. ► An alternative model is suggested.