The complex I from Rhodobacter capsulatus.
The NADH-ubiquinone oxidoreductase (type I NDH) of Rhodobacter capsulatus is a multisubunit enzyme encoded by the 14 genes of the nuo operon. This bacterial enzyme constitutes a valuable model for the characterization of the mitochondrial Complex I structure and enzymatic mechanism for the following reasons. (i) The mitochondria-encoded ND subunits are not readily accessible to genetic manipulation. In contrast, the equivalents of the mitochondrial ND1, ND2, ND4, ND4L, ND5 and ND6 genes can be easily mutated in R. capsulatus by homologous recombination. (ii) As illustrated in the case of ND1 gene, point mutations associated with human cytopathies can be reproduced and studied in this model system. (iii) The R. capsulatus model also allows the recombinant manipulations of iron-sulfur (Fe-S) subunits and the assignment of Fe-S clusters as illustrated in the case of the NUOI subunit (the equivalent of the mitochondrial TYKY subunit). (iv) Finally, like mitochondrial Complex I, the NADH-ubiquinone oxidoreductase of R. capsulatus is highly sensitive to the inhibitor piericidin-A which is considered to bind to or close to the quinone binding site(s) of Complex I. Therefore, isolation of R. capsulatus mutants resistant to piericidin-A represents a straightforward way to map the inhibitor binding sites and to try and define the location of quinone binding site(s) in the enzyme. These illustrations that describe the interest in the R. capsulatus NADH-ubiquinone oxidoreductase model for the general study of Complex I will be critically developed in the present review.
Dupuis
A
A
Laboratoire de BioEnergétique Cellulaire et Pathologique (BECP), EA 2019 UJF, Département de Biologie Moléculaire et Structurale CEA-grenoble, 17 rue des Martyrs, 38054 Grenoble Cedex 9, France. dupuis@aup.ceng.cea.fr
Chevallet
M
M
Darrouzet
E
E
Duborjal
H
H
Lunardi
J
J
Issartel
J P
JP
D000595:Amino Acid Sequence; D008969:Molecular Sequence Data; D016660:NAD(P)H Dehydrogenase (Quinone); D016354:Rhodobacter capsulatus / Q000201:enzymology*
D016660:NAD(P)H Dehydrogenase (Quinone)