Cation transport by the respiratory NADH:quinone oxidoreductase (complex I): facts and hypotheses

The respiratory complex I (electrogenic NADH:quinone oxidoreductase) has been considered to act exclusively as a H⁺ pump. This was questioned when the search for the NADH-driven respiratory Na⁺ pump in Klebsiella pneumoniae initiated by Peter Dimroth led to the discovery of a Na⁺-translocating complex in this enterobacterium. The 3D structures of complex I from different organisms support the idea that the mechanism of cation transport by complex I involves conformational changes of the membrane-bound NuoL, NuoM and NuoN subunits. In vitro methods to follow Na⁺ transport were compared with in vivo approaches to test whether complex I, or its individual NuoL, NuoM or NuoN subunits, extrude Na⁺ from the cytoplasm to the periplasm of bacterial host cells. The truncated NuoL subunit of the Escherichia coli complex I which comprises amino acids 1–369 exhibits Na⁺ transport activity in vitro. This observation, together with an analysis of putative cation channels in NuoL, suggests that there exists in NuoL at least one continuous pathway for cations lined by amino acid residues from transmembrane segments 3, 4, 5, 7 and 8. Finally, we discuss recent studies on Na⁺ transport by mitochondrial complex I with respect to its putative role in the cycling of Na⁺ ions across the inner mitochondrial membrane.