InterPro domain: IPR037225

Among the many polypeptide subunits that make up complex I, there is one with a molecular weight of 51kDa (in mammals), which is the second largest subunit of complex I [ 1 ]. The 51kDa subunit, as the corresponding bacterial subunit (Nqo1 in Thermus and NuoF in E. coli) [ 2 ], contains the NADH-binding site, the primary electron acceptor FMN-binding site, and a 4Fe-4S cluster [ 3 ].

NADH:ubiquinone oxidoreductase (complex I) ( 7.1.1.2 ) 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) [ 4 ]. 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 [ 5 ], 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 [ 6 ].

This superfamily represents the FMN-binding domain. Its structure is composed of three layers (alpha/beta/alpha) with parallel beta-sheet of four strands.

1. The respiratory-chain NADH dehydrogenase (complex I) of mitochondria. Eur. J. Biochem. 197, 563-76
2. The proton-translocating NADH-quinone oxidoreductase in the respiratory chain: the secret unlocked. Biochemistry 42, 2266-74
3. Structure of the hydrophilic domain of respiratory complex I from Thermus thermophilus. Science 311, 1430-6
4. The NADH:ubiquinone oxidoreductase (complex I) of respiratory chains. Q. Rev. Biophys. 25, 253-324
5. The respiratory complex I of bacteria, archaea and eukarya and its module common with membrane-bound multisubunit hydrogenases. FEBS Lett. 479, 1-5
6. Assembly of the Escherichia coli NADH:ubiquinone oxidoreductase (complex I). Biochim. Biophys. Acta 1777, 735-9