The coupling mechanism of mammalian respiratory complex I

Secrets of a proton pumping machine Mitochondrial complex I serves as a primary entry point for electrons from the tricarboxylic acid cycle into the mitochondrial electron transport chain. This massive, membrane-embedded protein complex must couple quinone reduction to conformational changes across more than 150 angstroms within four separate proton pumps. Kampjut et al. determined five structures of complex I in states along the catalytic cycle, a deactive conformation, and one with the inhibitor rotenone bound. The resolution of some structures was sufficient to see water molecules and to trace putative paths for proton transfer within the proton-pumping membrane domain. The structures add valuable details that provide a basis for generating mechanistic hypotheses for this crucial complex. Science , this issue p. eabc4209