NADH: ubiquinone oxidoreductase Complex

Electrons from NADH, together with two protons, are transferred to ubiquinone to form ubiquinol by complex I (NADH ubiquinone oxidoreductase). Complex I... 

In the mitochondria, ONOO- can mediate damage to OXPHOS by nitrosylat-ing/oxidizing tyrosine or thiol functional groups, rendering catalytic inactivation of complex I [NADH ubiquinone oxidoreductase], complex II [succinate ubiquinone oxidoreductase] and complex V (FI, FO-ATPase), thereby impeding ETC/ OXPHOS... 

Albracht SPJ, Hedderich R. 2000. Learning from hydrogenases location of a proton pump and of a second FMN in bovine NADH ubiquinone oxidoreductase (complex I) FEBS Lett 485 1-6. 

Gabaldon T, Rainey D, Huynen MA (2005) Tracing the evolution of a large protein complex in the eukaryotes, NADH ubiquinone oxidoreductase (complex I). J Mol Biol 348 857-870... 

Friedrich, T., VanHeek, P., Leif, H., Ohnishi, T., Forche, E., Kunze, B., Jansen, R., Trowitzsch-Kienast, W., Holfe, G., Reichenbach, H., and Weiss, H. Two binding sites of inhibitors in NADH ubiquinone oxidoreductase (complex I) relationship of one site with the ubiquinone oxido-reductase. Eur. J. Biochem., 219, 691, 1994. 

Brandt, U. (1997) Proton-translocation by membrane-bound NADH ubiquinone-oxidoreductase (complex I) through redoxgated ligand conduction. Biochim Biophys. Acta 1318, 79-91. Advanced discussion of models for electron movement through Complex I. 

Figure 18-7 Three-dimensional image of bovine NADH-Ubiquinone oxidoreductase (complex I) reconstructed from individual images obtained by electron cyro-microscopy.

Engler M, Anke T, Sterner O, Brandt U (1997) Pterulinic Acid and Pterulone, Two Novel Inhibitors of NADH Ubiquinone Oxidoreductase (Complex I) Produced by a Pterula Species I. Production, Isolation and Biological Activities. J Antibiot 50 325... 

T Yagi, Y Hatefi. Identification of the dicyclohexylcarbodiimide-binding subunit of NADH-ubiquinone oxidoreductase (Complex I). J Biol Chem 263 16150-16155, 1988. 

Figure 7-1. Pathways of fuel metabolism and oxidative phosphorylation. Pyruvate may be reduced to lactate in the cytoplasm or may be transported into the mitochondria for anabolic reactions, such as gluconeogenesis, or for oxidation to acetyl-CoA by the pyruvate dehydrogenase complex (PDC). Long-chain fatty acids are transported into mitochondria, where they undergo [ -oxidation to ketone bodies (liver) or to acetyl-CoA (liver and other tissues). Reducing equivalents (NADH, FADII2) are generated by reactions catalyzed by the PDC and the tricarboxylic acid (TCA) cycle and donate electrons (e ) that enter the respiratory chain at NADH ubiquinone oxidoreductase (Complex 0 or at succinate ubiquinone oxidoreductase (Complex ID- Cytochrome c oxidase (Complex IV) catalyzes the reduction of molecular oxygen to water, and ATP synthase (Complex V) generates ATP fromADP Reprinted with permission from Stacpoole et al. (1997).

N. Grigorieff. 1998. Three-dimensional structure of bovine NADH ubiquinone oxidoreductase (complex I) at 22 A in ice J. Mol. Biol. 211 1033-1046. (PubMed)... 

Grigorieff, N. 1999. Structure of the respiratory NADH ubiquinone oxidoreductase (complex 1). Curr. Opin. Struct. Biol. 9 476-483. 

In metazoans, the electron transport chain consists of four integral membrane complexes localized to the inner mitochondrial membrane complex I (NADH-ubiquinone oxidoreductase), complex II (succinate-ubiquinone oxidoreductase), complex III (ubiquinol-cytochrome c oxidoreductase) and complex IV (cytochrome c oxidase), plus coenzyme Q (ubiquinone) and cytochrome c. As first shown by Fry and Beesley (1991), the plasmodial electron transport chain differs from the metazoan system in lacking complex I however, a single subunit NADH dehydrogenase is present and is homologous to that found in plants, bacteria and yeast but not in animals (Krungkrai, 2004 Vaidya, 2004,2005 van Dooren et al., 2006). 

Synthesis and Inhibitory Action of Novel Acetogenin Mimics Alac-Acetogenins A New Class of Inhibitors of Mitochondrial NADH-Ubiquinone Oxidoreductase (Complex-I)... 

When mitochondria from bovine heart were solubilized by treatment with mild detergents it was possible to separate and purify the sections of the respiratory chain referred to earlier as coupling sites 1, 2 and 3. These were named Complex I (NADH-ubiquinone oxidoreductase), Complex III (ubiquinol-cytochrome c ox-idoreductase, cytochrome bci complex) and Complex IV (cytochrome c oxidase) [17], and have since been characterized as independent entities, although it is now recognized that these three complexes co-assemble with specific stoichiometry to form respiratory chain supercomplexes or respirasomes in fungal, plant and mammalian mitochondria [18-20]. There is also evidence that succinate-ubiquinone oxidoreductase (which was purified alongside the other complexes and named Complex II [21]) forms a tight association with Complex III in yeast mitochondria [22]. 

N. Grigorieff, Three-dimensional Structure of Bovine NADH Ubiquinone Oxidoreductase (Complex I) at 22 A in Ice. J. Mol Biol, 277, 1033-1048,1998. 

B. Bottcher, D. Scheide, M. Hasterberg, L. Nagel-Stegerand, and T. Friedrich, A Novel, Enzymatically Active Conformation of the Escherichia coli NADH Ubiquinone Oxidoreductase (Complex I). J. Biol Chem., 2TJ,... 

The last pesticide from this section is Flufenerim (Flumfen 302), which is under development by Ube Industries as an insecticide. It is reported to control aphids, whiteflies, and cotton leafworm, but has no activity against thrips [296]. Since Flufenerim is chemically related to Pyrimidifen (Miteclean 369) (Fig. 16), it was initially believed to have similar mechanism of action, i.e. inhibition of the mitochondrial electron transport of NADH dehydrogenase (NADH ubiquinone oxidoreductase, complex I) - an enzyme which transfers electrons from NADH to ubiquinone and hence opens the electron transport chain cascade. Nevertheless, it was shown that 302 reduced activity of acetylcholinesterase - an effect which possibly can be addressed to interaction with other systems [297]. 

Because of the known action of taxol, Manzano et al. [137] initiated state 3 respiration in isolated mitochondria by the addition of 0.8 mM ADP together with one specific substrate of each respiratory chain complex. These were 10 mM pyruvate (NADH-ubiquinone oxidoreductase, complex I), 1 mM succinate (succinate dehydrogenase, complex II) or 0.2 mM ascorbate and 10 pM tetramethyl-/7-phenylenediamine (cytochrome oxidase). The addition of taxol strongly reduced the respiratory capacity of complex I and complex II by 58% and 45%, respectively, without affecting cytochrome oxidase. Thus, they found a direct effect on respiratory metabolism. This is presumably because the change to mitochondrial bcl protein in the intermembrane space caused the release of cytochrome c [138] and can lead to the apoptotic cascade (see Section 5,2.2). 

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