NADH-ubiquinone oxidoreductase (complex I, or Nuo) (EC:1.6.5.3) is a respiratory-chain enzyme that catalyses the transfer of two electrons from NADH to ubiquinone in a reaction that is associated with proton translocation across the membrane (NADH + ubiquinone = NAD+ + ubiquinol) PMID:1470679. Complex I is a major source of reactive oxygen species (ROS) that are predominantly formed by electron transfer from FMNH(2). Complex I is found in bacteria, cyanobacteria (as a NADH-plastoquinone oxidoreductase), archaea PMID:10940377, mitochondria, and in the hydrogenosome, a mitochondria-derived organelle. In general, the bacterial complex consists of 14 different subunits, while the mitochondrial complex contains homologues to these subunits in addition to approximately 31 additional proteins PMID:18394423.

This superfamily entry represents chain 6 from NADH-ubiquinone oxidoreductase and NADH-plastoquinone oxidoreductase. Bacterial proton-translocating NADH-quinone oxidoreductase (NDH-1) is composed of 14 different subunits. The chain belonging to this family is a subunit that constitutes the membrane sector of the complex. It reduces ubiquinone to ubiquinol utilising NADH. Plant chloroplastic NADH-plastoquinone oxidoreductase reduces plastoquinone to plastoquinol. Mitochondrial NADH-ubiquinone oxidoreductase from a variety of sources reduces ubiquinone to ubiquinol.

Subunit NuoJ has an unusual non-globular fold: three linearly arranged amino-terminal TM helices border NuoK, and TMs 4 and 5 are separated at the opposite sides of the domain. Thus, NuoJ interweaves between NuoK, A and N, stabilising the complex. TM3 of NuoJ contains in its middle a pi-bulge/kink (residues 59-62), so this helix is probably flexible and mechanistically important. TM3 is the most conserved helix in NuoJ and is a hotspot for human mitochondrial disease mutations.

PFAM:PF00499, INTERPRO:IPR001457,DOI:10.1038/nature10330