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3.D.1 The H+ or Na+-translocating NADH Dehydrogenase (NDH) Family

NADH:ubiquinone oxidoreductases type I (NDH-Is) of bacteria and of eukaryotic mitochondria and chloroplasts couple electron transfer to the electrogenic transport of protons (Brandt, 2006) or Na+ (Gemperli, et al., 2007). The subunit, NuoL, is related to Na+/ H+antiporters of 2.A.63.1.1 (PhaA and PhaD). NuoL has been shown to transport Na+ and K+ independently of other Nuo subunits (Gemperli et al., 2007). These protein complexes are multi-subunit complexes with 13 or 14 recognized subunits in the E. coli or P. denitrificans complex and about 30-50 distinct subunits in the complexes of eukaryotic mitochondria.  The structures and mechanisms of respiratory I have been reviewed (Sazanov 2015).  There is a probable link between redox changes at heme a and modulation of intramolecular proton-transfer rates (Vilhjálmsdóttir et al. 2015).  Respiratory complexes I, III and IV form a complex, and it's archetecture has been studied (Gu et al. 2016).

Complex I contains a ubiquinone binding pocket at the interface of the 49-kDa and PSST subunits. Close to iron-sulfur cluster N2, the proposed immediate electron donor for ubiquinone, a highly conserved tyrosine constitutes a critical element of the quinone reduction site. A possible quinone exchange path leads from cluster N2 to the N-terminal beta-sheet of the 49-kDa subunit (Tocilescu et al., 2010). All 45 subunits of the bovine NDHI have been sequenced (Cardol et al., 2004; Gabaldon et al., 2005). Each complex contains noncovalently bound FMN, coenzyme Q and several iron-sulfur centers. The bacterial NDHs have 8-9 iron-sulfur centers. Electrons pass from NADH to FMN, to the various iron-sulfur centers, and finally to ubiquinone or another quinone. NDHI, a complex I in mitochondria, forms a 'supercomplex' with complex III (3.D.3) and complex IV (3.D.4) (Schafer et al., 2007). The mechanistic details are discussed by Hirst (2010). The interaction of mitochondrial complex I with complex III is discussed by Dudkina et al. (2009). The x-ray structures of the functional modules of the 40 subunit Yarrowia lipolytica Complex I have been examined, and the basis for conformational coupling has been presented (Hunte et al., 2010).  Moreover, a molecular mechanism of the proton pump has been proposed (Verkhovskaya and Bloch 2013).

The positions of all iron-sulfur clusters relative to the membrane arm were determined in the complete enzyme complex. The ubiquinone reduction site resides close to 30 Å above the membrane domain. The arrangement of functional modules suggests conformational coupling of redox chemistry with proton pumping and essentially excludes direct mechanisms. (Hunte et al., 2010) suggest that a ~60 Å long helical transmission-element is critical for transducing conformational energy to proton-pumping elements in the distal module of the membrane arm.  The x-ray structures of various complexes have been solved, and a coupling mechanism involving long range conformational changes has been proposed (Sazanov et al. 2013).

The mammalian enzyme complexes contain several water soluble peripheral membrane proteins which are anchored to the integral membrane constituents. The seven most hydrophobic proteins of the complex are encoded within mammalian or fungal mitochondrial genomes while the remainder are nuclearly encoded (Brandt, 2006; Gray et al., 2004). All thirteen of the E. coli proteins, which comprise NADH dehydrogenase I and are encoded within the nuo operon, are homologous to mitochondrial complex I subunits. Fearnley and Walker (1992) have provided multiple alignments and hydropathy plots for many of the NDH complex subunits, but phylogenetic analyses are not included. NDH-I complexes contrast with NDH-II complexes that do not transport H+ or Na+.

Efremov et al. (2010) have determined the structure of the E. coli NDH-I transmembrane structure at 3.9 A resolution. The antiporter-like subunits NuoL/M/N each contains 14 conserved transmembrane (TM) helices. Two of them are discontinuous, but subunit NuoL contains a 110-A long amphipathic α-helix, spanning the entire length of the domain. The structure of the entire complex I from Thermus thermophilus at 4.5 A resolution reveals an L-shaped assembly with 63 TM helices. The architecture of the complex suggests that the conformational changes at the interface of the two main domains drives the long amphipathic α-helix of NuoL in a piston-like motion, tilting nearby discontinuous TM helices, resulting in proton translocation (Efremov et al., 2010). This work has been reviewed and evaluated (Efremov and Sazanov, 2011b).

The NDH family includes complexes in bacteria, archaea and eukaryotic organelles (mitochondria and chloroplasts) that may use different electron donors. Thus, the bacterial and mitochondrial complexes function as NADH dehydrogenases, but some of the archaeal complexes function as F420H2 dehydrogenases (see TC# 3.D.9). The electron donor(s) for the cyanobacterial and plastid complexes is (are) not yet known. Despite the potentially different electron input sites, eleven polypeptide chains constitute the structural framework for proton translocation and quinone binding. At least six of these subunits are also present in a family of membrane-bound multisubunit [NiFe] hydrogenases. One of these hydrogenases (from Paracoccus furiosus) has been shown to couple electron transfer to H+ translocation (Friedrich and Scheide, 2000; Sapra et al., 2003). In E. coli these hydrogenases are hydrogenases 3 and 4 of the formate hydrogen lyase system. They also include the CO-induced hydrogenase of Rhodospirillum rubrum and the Ech hydrogenase of Methanosarcina barkerei. The archaeal hydrogenase transfers reducing equivalents generated by the oxidation of the low potential electron donor ferridoxin to protons, yielding H2, coupled to the generation of a pmf (Sapra et al., 2003). Several archaea have two such enzymes of unknown physiological function.

Campylobacter jejuni encodes 12 of the 14 subunits that make up the respiratory NADH ubiquinone oxidoreductase (complex I). The two nuo genes not present in C. jejuni encode the NADH dehydrogenase, and in their place in the operon are the novel genes designated as Cj1575c (CAL25672) and Cj1574c (CAL35671; 24% identical and 41% similar (e-5) to ORF1 of plasmid pIP501 (3.A.7.14.1)). Mutants were generated in which each of the 12 nuo genes (homologues to known complex I subunits) were disrupted or deleted (Weerakoon and Olson, 2008). Each of the nuo mutants do not grow in amino acid-based media unless supplemented with an alternative respiratory substrate such as formate. Unlike the nuo genes, Cj1574c is an essential gene and could not be disrupted unless an intact copy of the gene was provided at an unrelated site on the chromosome. A nuo deletion mutant can efficiently respire formate but is deficient in α-ketoglutarate respiratory activity when compared to wild type cells. In C. jejuni, α-ketoglutarate respiration is mediated by 2-oxoglutarate:acceptor oxidoreductase. Mutagenesis of this enzyme abolished α-ketoglutarate-dependent O2 uptake and failed to reduce the electron transport chain. The electron acceptor for this 2-oxoglutarate oxidoreductase was determined to be flavodoxin, which was also found to be an essential protein in C. jejuni. A model was presented by Weerakoon and Olson (2008) in which CJ1574 mediates electron flow into the respiratory transport chain from reduced flavodoxin and through complex I to ubiquinone.

Oxidation of NADH by submitochondrial particles (SMPs) from the yeast Yarrowia lipolytica is coupled to protonophore-resistant Na+ uptake, indicating that a redox-driven, primary Na+ pump is operative in the inner mitochondrial membrane. A respiratory NADH dehydrogenase couples NADH-dependent reduction of ubiquinone to Na+ translocation. NADH-driven Na+ transport was sensitive rotenone, a specific inhibitor of complex I (Lin et al., 2008).

E. coli complex I (NADH dehydrogenase) is capable of proton translocation in the same direction to the established Δψ, showing that in the tested conditions, the coupling ion is H+ (Batista and Pereira 2011). Na+ transport in the opposite direction was observed, and although Na+ was not necessary for the catalytic or proton transport activities, its presence increased the latter. H+ was translocated by the P. denitrificans complex I, but in this case, H+ transport was not influenced by Na+, and Na+ transport was not observed. Possibly, the E. coli complex I has two energy coupling sites (one Naindependent and the other Na+ dependent), as observed for the Rhodothermus marinus complex I, whereas the coupling mechanism of the P. denitrificans enzyme is completely Na+ independent. It is also possible that another transporter catalyzes the uptake of Na+.  Complex I energy transduction by proton pumping may not be exclusive to the R. marinus enzyme. The Na+/H+ antiport activity seems not to be a general property of complex I (Batista and Pereira 2011). 

The NADH-driven respiratory Na+ pump in Klebsiella pneumoniae was first reported by Peter Dimroth and co-workers (Steffen and Steuber 2013). 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. A truncated NuoL subunit of the E. coli complex 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, Na+ transport by mitochondrial complex I has been discussed with respect to its possible role in the cycling of Na+ across the inner mitochondrial membrane (Steffen and Steuber 2013).

Three of the conserved, membrane-bound subunits in NADH dehydrogenase are related to each other, and to Mrp sodium-proton antiporters. Structural analysis of two prokaryotic complexes I revealed that the three subunits each contain fourteen transmembrane helices that overlay in structural alignments: the translocation of three protons may be coordinated by a lateral helix connecting them together (Efremov et al., 2010). The architecture of respiratory complex I. Nature 465, 441-447). Birrel & Hirst (2010) showed that in higher metazoans the threefold symmetry is broken by the loss of three helices from subunit ND2.

M. mazei and M. barkeri belong to the group of aceticlastic methanogens and converts acetate into the potent greenhouse gases CO2 and CH4. The aceticlastic respiratory chain involved in methane formation comprises the three transmembrane proteins Ech hydrogenase, F(420) nonreducing hydrogenase and heterodisulfide reductase. All three contribute to the proton motive force. ATP synthesis was observed in a cytoplasm-free vesicular system that was dependent on the oxidation of reduced ferredoxin and the formation of molecular hydrogen (Welte et al., 2010). ATP formation was not observed in a deletion mutant strain. Proton protonophores led to complete inhibition of ATP formation without inhibiting hydrogen production, whereas sodium ion ionophores did not affect ATP formation. Welte et al. (2010) concluded that the Ech hydrogenase complex acts as a primary proton pump in a ferredoxin-dependent electron transport system.

Efremov and Sazanov (2011) have reported the crystal structure of the membrane domain of complex I at 3.0 Å resolution. It includes six subunits, NuoL, NuoM, NuoN, NuoA, NuoJ and NuoK, with 55 transmembrane helices. The fold of the homologous antiporter-like subunits L, M and N is novel, with two inverted structural repeats of five transmembrane helices arranged, unusually, face-to-back. Each repeat includes a discontinuous transmembrane helix and forms half of a channel across the membrane. A network of conserved polar residues connects the two half-channels, completing the proton translocation pathway. Unexpectedly, lysines rather than carboxylate residues act as the main elements of the proton pump in these subunits. The fourth probable proton-translocation channel is at the interface of subunits N, K, J and A. The structure indicates that proton translocation in complex I, uniquely, involves coordinated conformational changes in six symmetrical structural elements.

The architecture of the hydrophobic region of complex I shows multiple proton transporters that are mechanically interlinked. Transduction of conformational changes to drive the transmembrane transporters linked by a 'connecting rod' during the reduction of ubiquinone (Q) can account for two or three of the four protons pumped per NADH oxidized. The remaining proton must be pumped by direct coupling at the Q-binding site. Treberg et al. (2011) proposed direct and indirect coupling mechanisms to account for the pumping of the four protons.

The first crystal structure of the entire, intact complex I (from Thermus thermophilus) at 3.3 A resolution has been reported (Baradaran et al. 2013). The structure of the 536-kDa complex comprises 16 different subunits, with a total of 64 transmembrane helices and 9 iron-sulphur clusters. The core fold of subunit Nqo8 (ND1 in humans) is, unexpectedly, similar to a half-channel of the antiporter-like subunits. Small subunits nearby form a linked second half-channel, which completes the fourth proton-translocation pathway (present in addition to the channels in three antiporter-like subunits). The quinone-binding site is unusually long, narrow and enclosed. The quinone headgroup binds at the deep end of this chamber, near iron-sulphur cluster N2. The chamber is linked to the fourth channel by a 'funnel' of charged residues. The link continues over the entire membrane domain as a flexible central axis of charged and polar residues, and probably has a leading role in the propagation of conformational changes, aided by coupling elements. The structure suggests that a unique, out-of-the-membrane quinone-reaction chamber enables the redox energy to drive concerted long-range conformational changes in the four antiporter-like domains, resulting in translocation of four protons per cycle (Baradaran et al., 2013). 

The x-ray structure of mitochondrial complex I has been solved at a resolution of 3.6 to 3.9 angstroms, describing in detail the central subunits that execute the bioenergetic function (Zickermann et al. 2015). A continuous axis of basic and acidic residues running centrally through the membrane arm connects the ubiquinone reduction site in the hydrophilic arm to four putative proton-pumping units. The binding position for a substrate analogous inhibitor and blockage of the predicted ubiquinone binding site provide a model for the 'deactive' form of the enzyme. The proposed transition into the active form is based on a concerted structural rearrangement at the ubiquinone reduction site, providing support for a two-state stabilization-change mechanism of proton pumping (Zickermann et al. 2015).  The largest membrane-embedded subunits, ND5, ND4, and ND2, share a similar core of 14 TMSs with two repeats of five TMHs (A, TMH4–8; B, TMH9–13) in inverted topology. Each repeat features a discontinuous helix (TMH7a/b, TMH12a/b). Such helices are hallmarks of ion-translocating membrane proteins (Zickermann et al. 2015). Indeed, ND5, ND4, and ND2 are homologous to the Mrp Na+/H+ antiporter family, which suggests a role in proton pumping (Zickermann et al. 2015). ND5 has a C-terminal extension with a lateral helix, >60 Å long, lining ND5, ND4, and ND2 on the concave side of the arm close to the matrix side. The C terminus of ND5 is anchored to ND2 via a V-shaped arrangement of TMSs 16 and 17. The lateral helix was previously identified in the low-resolution analysis of mitochondrial complex I from Y. lipolytica, and is also present in the bacterial and bovine complexes in which its C terminus is anchored by one TMS only.  

Berrisford et al. 2016; have solved the crystal structures of the hydrophilic domain of complex I from Thermus thermophilus, the membrane domain from Escherichia coli and more recently of the intact, entire complex I from T. thermophilus (536 kDa, 16 subunits, 9 iron- sulphur clusters, 64 transmembrane helices). The 95 Å long electron transfer pathway through the enzyme proceeds from the primary electron acceptor flavin mononucleotide through seven conserved Fe-S clusters to the unusual elongated quinone-binding site at the interface with the membrane domain. Four putative proton translocation channels are found in the membrane domain, all linked by the central flexible axis containing charged residues. The redox energy of electron transfer is coupled to proton translocation by the as yet undefined mechanism proposed to involve long-range conformational changes.


The generalized transport reactions catalyzed by NDH family members are:

NADH + ubiquinone + 4H+ (in) → NAD+ + ubiquinol + 4H+ (out)


This family belongs to the: Na+ Transporting Mrp Superfamily.

References associated with 3.D.1 family:

Bagramyan, K., A. Vassilian, N. Mnatsakanyan, and A. Trchounian. (2001). Participation of hyf-encoded hydrogenase 4 in molecular hydrogen release coupled with proton-potassium exchange in Escherichia coli. Membr Cell Biol 14: 749-763. 11817571
Bagramyan, K., N. Mnatsakanyan, A. Poladian, A. Vassilian, and A. Trchounian. (2002). The roles of hydrogenases 3 and 4, and the F0F1-ATPase, in H2 production by Escherichia coli at alkaline and acidic pH. FEBS Lett. 516: 172-178. 11959127
Baradaran, R., J.M. Berrisford, G.S. Minhas, and L.A. Sazanov. (2013). Crystal structure of the entire respiratory complex I. Nature 494: 443-448. 23417064
Barquera, B., P. Hellwig, W. Zhou, J.E. Morgan, C.C. Häse, K.K. Gosink, M. Nilges, P.J. Bruesehoff, A. Roth, C.R.D. Lancaster, and R.B. Gennis. (2002). Purification and characterization of the recombinant Na+-translocating NADH:quinone oxidoreductase from Vibrio cholerae. Biochemistry 41: 3781-3789. 11888296
Batista, A.P. and M.M. Pereira. (2011). Sodium influence on energy transduction by complexes I from Escherichia coli and Paracoccus denitrificans. Biochim. Biophys. Acta. 1807: 286-292. 21172303
Berrisford, J.M., R. Baradaran, and L.A. Sazanov. (2016). Structure of bacterial respiratory complex I. Biochim. Biophys. Acta. 1857: 892-901. 26807915
Birrell, J.A. and J. Hirst. (2010). Truncation of subunit ND2 disrupts the threefold symmetry of the antiporter-like subunits in complex I from higher metazoans. FEBS Lett. 584: 4247-4252. 20846527
Brandt, U. (1997). Proton-translocation by membrane-bound NADH:ubiquinone-oxidoreductase (complex I) through redox-gated ligand conduction. Biochim Biophys Acta 1318: 79-91. 9030257
Brandt, U. (2006). Energy converting NADH:quinone oxidoreductase (complex I). Annu. Rev. Biochem. 75:69-92. 16756485
Cardol, P., F. Vanrobaeys, B. Devreese, J. Van Beeumen, R.F. Matagne, and C. Remacle. (2004). Higher plant-like subunit composition of mitochondrial complex I from Chlamydomonas reinhardtii: 31 conserved components among eukaryotes. Biochim. Biophys. Acta. 1658:212-224. 15450959
Dudkina NV., Kouril R., Peters K., Braun HP. and Boekema EJ. (2010). Structure and function of mitochondrial supercomplexes. Biochim Biophys Acta. 1797(6-7):664-70. 20036212
Efremov, R.G. and L.A. Sazanov. (2011). Respiratory complex I: 'steam engine' of the cell? Curr. Opin. Struct. Biol. 21: 532-540. 21831629
Efremov, R.G. and L.A. Sazanov. (2011). Structure of the membrane domain of respiratory complex I. Nature 476: 414-420. 21822288
Efremov, R.G., R. Baradaran, and L.A. Sazanov. (2010). The architecture of respiratory complex I. Nature 465: 441-445. 20505720
Fearnley, I.M. and J.E. Walker. (1992). Conservation of sequences of subunits of mitochondrial complex I and their relationships with other proteins. Biochim. Biophys. Acta 1140: 105-134. 1445936
Forzi, L., J. Koch, A.M. Guss, C.G. Radosevich, W.W. Metcalf, and R. Hedderich. (2005). Assignment of the [4Fe-4S] clusters of Ech hydrogenase from Methanosarcina barkeri to individual subunits via the characterization of site-directed mutants. FEBS J. 272: 4741-4753. 16156794
Fox, J.D., R.L. Kerby, G.P. Roberts, and P.W. Ludden. (1996b). Characterization of the CO-induced, CO-tolerant hydrogenase from Rhodospirillum rubrum and the gene encoding the large subunit of the enzyme. J. Bacteriol. 178: 1515-1524. 8626276
Fox, J.D., Y. He, D. Shelver, G.P. Roberts, and P.W. Ludden. (1996a). Characterization of the region encoding the CO-induced hydrogenase of Rhodospirillum rubrum. J. Bacteriol. 178: 6200-6208. 8892819
Friedrich, T. (1998). The NADH:ubiquinone oxidoreductase (complex I) from Escherichia coli. Biochim. Biophys. Acta 1364: 134-146. 9593861
Friedrich, T. and D. Scheide. (2000). The respiratory complex I of bacteria, archaea and eukarya and its module common with membrane-bound multisubunit hydrogenases. FEBS Lett. 479: 1-5. 10940377
Friedrich, T., B. Brors, P. Hellwig, L. Kintscher, T. Rasmussen, D. Scheide, U. Schulte, W. Mäntele, and H. Weiss. (2000). Characterization of two novel redox groups in the respiratory NADH: ubiquinone oxidoreductase (complex I). Biochim. Biophys. Acta 1459: 305-309. 11004444
Gabaldón, T., D. Rainey, and M.A. Huynen. (2005). Tracing the evolution of a large protein complex in the eukaryotes, NADH:ubiquinone oxidoreductase (Complex I). J. Mol. Biol. 348: 857-870. 15843018
Gemperli, A.C., C. Schaffitzel, C. Jakob, and J. Steuber. (2007). Transport of Na+ and K (+) by an antiporter-related subunit from the Escherichia coli NADH dehydrogenase I produced in Saccharomyces cerevisiae. Arch. Microbiol. 188: 509-521. 17583799
Gemperli, A.C., P. Dimroth, and J. Steuber. (2003). Sodium ion cycling mediates energy coupling between complex I and ATP synthase. Proc. Natl. Acad. Sci. USA 100: 839-844. 12538874
Gennis, R.B. and V. Stewart. (1996). Respiration. In: F.C. Neidardt et al. (eds.), Escherichia coli and Salmonella. Cellular and Molecular Biology, Vol. 1, 2nd Ed. Washington, DC: ASM Press, pp. 217-261.
Gray, M.W., B.F. Lang, and G. Burger. (2004). Mitochondria of protists. Annu. Rev. Genet. 38:477-524. 15568984
Grigorieff, N. (1999). Structure of the respiratory NADH:ubiquinone oxidoreductase (complex I). Curr. Opin. Struc. Biol. 9: 476-483. 10449365
Gu, J., M. Wu, R. Guo, K. Yan, J. Lei, N. Gao, and M. Yang. (2016). The architecture of the mammalian respirasome. Nature 537: 639-643. 27654917
Hedderich, R. and L. Forzi. (2005). Energy-converting [NiFe] hydrogenases: more than just H2 activation. J. Mol. Microbiol. Biotechnol. 10: 92-104. 16645307
Hirst, J. (2003). The dichotomy of complex I: a sodium ion pump or a proton pump. Proc. Natl. Acad. Sci. USA 100: 773-775. 12552138
Hirst, J. (2010). Towards the molecular mechanism of respiratory complex I. Biochem. J. 425: 327-339. 20025615
Hunte, C., V. Zickermann, and U. Brandt. (2010). Functional modules and structural basis of conformational coupling in mitochondrial complex I. Science 329: 448-451. 20595580
Ishikawa, N., A. Takabayashi, S. Ishida, Y. Hano, T. Endo, and F. Sato. (2008). NDF6: a thylakoid protein specific to terrestrial plants is essential for activity of chloroplastic NAD(P)H dehydrogenase in Arabidopsis. Plant Cell Physiol. 49: 1066-1073. 18535009
Krebs, W., J. Steuber, A.C. Gemperli, and P. Dimroth. (1999). Na+ translocation by the NADH: ubiquinone oxidoreductase (complex I) from Klebsiella pneumoniae. Mol. Microbiol. 33: 590-598. 10417649
Künkel, A., J.A. Vorholt, R.K. Thauer, and R. Hedderich. (1998). An Escherichia coli hydrogenase-3-type hydrogenase in methanogenic archaea. Eur. J. Biochem. 252: 467-476. 9546662
Lin, P.C., A. Puhar, and J. Steuber. (2008). NADH oxidation drives respiratory Na+ transport in mitochondria from Yarrowia lipolytica. Arch. Microbiol. 190: 471-480. 18551278
Lu, H. and X. Cao. (2008). GRIM-19 is essential for maintenance of mitochondrial membrane potential. Mol. Biol. Cell 19: 1893-1902. 18287540
McDowall, J.S., B.J. Murphy, M. Haumann, T. Palmer, F.A. Armstrong, and F. Sargent. (2014). Bacterial formate hydrogenlyase complex. Proc. Natl. Acad. Sci. USA 111: E3948-3956. 25157147
Nakamaru-Ogiso, E., M.C. Kao, H. Chen, S.C. Sinha, T. Yagi, and T. Ohnishi. (2010). The membrane subunit NuoL(ND5) is involved in the indirect proton pumping mechanism of Escherichia coli complex I. J. Biol. Chem. 285: 39070-39078. 20826797
Peng, L., H. Yamamoto, and T. Shikanai. (2011). Structure and biogenesis of the chloroplast NAD(P)H dehydrogenase complex. Biochim. Biophys. Acta. 1807: 945-953. 21029720
Sapra, R., K. Bagramyan, and M.W.W. Adams. (2003). A simple energy-conserving system: proton reduction coupled to proton translocation. Proc. Natl. Acad. Sci. USA 100: 7545-7550. 12792025
Sato, M., P.K. Sinha, J. Torres-Bacete, A. Matsuno-Yagi, and T. Yagi. (2013). Energy transducing roles of antiporter-like subunits in Escherichia coli NDH-1 with main focus on subunit NuoN (ND2). J. Biol. Chem. 288: 24705-24716. 23864658
Sazanov, L.A. (2015). A giant molecular proton pump: structure and mechanism of respiratory complex I. Nat Rev Mol. Cell Biol. 16: 375-388. 25991374
Sazanov, L.A., R. Baradaran, R.G. Efremov, J.M. Berrisford, and G. Minhas. (2013). A long road towards the structure of respiratory complex I, a giant molecular proton pump. Biochem Soc Trans 41: 1265-1271. 24059518
Schafer, E., N.A. Dencher, J. Vonck, and D.N. Parcej. (2007). Three-dimensional structure of the respiratory chain supercomplex I1III2IV1 from bovine heart mitochondria. Biochemistry. 46(44):12579-12585. 17927210
Soboh, B., D. Linder, and R. Hedderich. (2002). Purification and catalytic properties of a CO-oxidizing:H2-evolving enzyme complex from Carboxydothermus hydrogenoformans. Eur. J. Biochem. 269: 5712-5721. 12423371
Soboh, B., D. Linder, and R. Hedderich. (2004). A multisubunit membrane-bound [NiFe] hydrogenase and an NADH-dependent Fe-only hydrogenase in the fermenting bacterium Thermoanaerobacter tengcongensis. Microbiology 150: 2451-2463. 15256587
Steffen, W. and J. Steuber. (2013). Cation transport by the respiratory NADH:quinone oxidoreductase (complex I): facts and hypotheses. Biochem Soc Trans 41: 1280-1287. 24059520
Steuber, J., C. Schmid, M. Rufibach, and P. Dimroth. (2000). Na+ translocation by complex I (NADH: quinone oxidoreductase) of Escherichia coli. Mol. Microbiol. 35: 428-434. 10652103
Stroud, D.A., E.E. Surgenor, L.E. Formosa, B. Reljic, A.E. Frazier, M.G. Dibley, L.D. Osellame, T. Stait, T.H. Beilharz, D.R. Thorburn, A. Salim, and M.T. Ryan. (2016). Accessory subunits are integral for assembly and function of human mitochondrial complex I. Nature. [Epub: Ahead of Print] 27626371
Tocilescu MA., Zickermann V., Zwicker K. and Brandt U. (2010). Quinone binding and reduction by respiratory complex I. Biochim Biophys Acta. 1797(12):1883-90. 20493164
Treberg, J.R., C.L. Quinlan, and M.D. Brand. (2011). Evidence for two sites of superoxide production by mitochondrial NADH-ubiquinone oxidoreductase (complex I). J. Biol. Chem. 286: 27103-27110. 21659507
Verkhovskaya, M. and D.A. Bloch. (2013). Energy-converting respiratory Complex I: on the way to the molecular mechanism of the proton pump. Int J Biochem. Cell Biol. 45: 491-511. 22982742
Vilhjálmsdóttir, J., A.L. Johansson, and P. Brzezinski. (2015). Structural Changes and Proton Transfer in Cytochrome c Oxidase. Sci Rep 5: 12047. 26310633
Vinothkumar, K.R., J. Zhu, and J. Hirst. (2014). Architecture of mammalian respiratory complex I. Nature 515: 80-84. 25209663
Walker, J.E. (1992). The NADH:ubiquinone oxidoreductase (complex I) of respiratory chains. Quart. Rev. Biophys. 25: 253-324. 1470679
Weerakoon, D.R., and J.W. Olson. (2008). The Campylobacter jejuni NADH:ubiquinone oxidoreductase (complex I) utilizes flavodoxin rather than NADH. J. Bacteriol. 190: 915-925. 18065531
Weidner, U., S. Geier, A. Ptock, T. Friedrich, H. Leif, and H. Weiss. (1993). The gene locus of the proton-translocating NADH:ubiquinone oxidoreductase in Escherichia coli. J. Mol. Biol. 233: 109-122. 7690854
Welte C. and Deppenmeier U. (2014). Bioenergetics and anaerobic respiratory chains of aceticlastic methanogens. Biochim Biophys Acta. 1837(7):1130-47. 24333786
Welte, C., C. Krätzer, and U. Deppenmeier. (2010). Involvement of Ech hydrogenase in energy conservation of Methanosarcina mazei. FEBS J. 277: 3396-3403. 20629748
Yagi, T., T. Yano, and A. Matsuno-Yagi. (1993). Characteristics of the energy-transducing NADH-quinone oxidoreductase of Paracoccus denitrificans as revealed by biochemical, biophysical and molecular biological approaches. J. Bioener. Biomembr. 25: 339-345. 8226715
Yagi, T., T. Yano, S. Di Bernardo, and A. Matsuno-Yagi. (1998). Procaryotic complex I (NDH-1), an overview. Biochim. Biophys. Acta 1364: 125-133. 9593856
Zickermann, V., C. Wirth, H. Nasiri, K. Siegmund, H. Schwalbe, C. Hunte, and U. Brandt. (2015). Structural biology. Mechanistic insight from the crystal structure of mitochondrial complex I. Science 347: 44-49. 25554780