Abstract
The modern-day respiratory complex I shares a common ancestor with the membrane-bound hydrogenase (MBH) and membrane-bound sulfane sulfur reductase (MBS). MBH and MBS use protons and sulfur as their respective electron sinks, which helped to conserve energy during early life in the Proterozoic era when the Earth's atmosphere was low in oxygen. MBH and MBS likely evolved from an integration of an ancestral, membrane-embedded, multiple resistance and pH antiporter and a soluble redox-active module encompassing a [NiFe] hydrogenase. In this review, we discuss how the structures of MBH, MBS, multiple resistance and pH, photosynthetic NADH dehydrogenase-like complex type-1, and complex I, which have been determined recently, thanks to the advent of high-resolution cryo-EM, have significantly improved our understanding of the catalytic reaction mechanisms and the evolutionary relationships of the respiratory complexes.