Chapter 1The energy-transducing NADH: quinone oxidoreductase, complex I
Section snippets
Complex I in the oxidative phosphorylation system
NADH: ubiquinone oxidoreductase (EC 1.6.5.3), complex I, is a large and very complicated membrane-bound multi-subunit enzyme complex that plays an important role in energy production by the mitochondrial oxidative phosphorylation system (OXPHOS) (Fig. 1(a)). Complex I is located at an entry point of the electron transport chain and initiates electron transfer by oxidizing NADH and the electrons are transferred to a lipid-soluble electron carrier quinone (coenzyme Q) as an electron acceptor.
Overall structure – two distinct domains and different functions
A high-resolution 3D structure of complex I remains to be determined. Currently, low-resolution structure electron microscopic images of complex I from several sources are available (Guènebaut et al., 1997; Grigorieff, 1998; Guènebaut et al., 1998; Djafarzadeh et al., 2000). Complex I appears to have an “L-shape” and this unique figure is conserved between eukaryote and prokaryote complex I. The enzyme is made of two major parts: a hydrophilic promontory (peripheral) part extruding from the
Kinetic measurements
As has been frequently mentioned, it is difficult to accurately assess the activity of complex I (Lenaz, 1998; Vinogradov, 1998). Complex I activity is generally measured using Q analogues such as UQ-1, UQ-2, or DB as a substrate of endogenous electron acceptors. However, most of these Q analogues accept electrons from non-physiological sites and NADH: quinone oxidoreductase and proton pump activities are different from one Q analogue to another (Degli Esposti et al., 1996). The paucity of
Evolution of complex I: new insights into the structure and function relationship
A rapidly growing genomic sequence database is a valuable source of information and has provided new insight into the structure–function relationship of complex I. A striking similarity of complex I family to the [NiFe] hydrogenases was found, suggesting that they share a common ancestor. Based upon exhaustive sequence analyses, Friedrich and his co-workers proposed an evolutionary scheme of complex I (Friedrich and Weiss, 1997; Friedrich and Scheide, 2000). The “Modular evolution hypothesis”
Energy-coupling mechanism
The mechanism by which complex I utilizes the redox energy to translocate cations such as H+ or Na+ ions across the membrane is still unknown. To date, several energy-coupling hypotheses have been proposed for complex I (Mitchell, 1966; Ohnishi and Salerno, 1982; Krishnamoorthy and Hinkle, 1988; Ragan, 1990; Weiss and Friedrich, 1991; Vinogradov, 1993; Degli Esposti and Ghelli, 1994; Brandt, 1997, Brandt, 1999; Dutton et al., 1998). Recent models proposed by Brandt and by Dutton et al. assume
Neurodegenerative disease associates with complex I
A number of devastating neurodegenerative disorders have been found in connection with the defects of OXPHOS. Considering the fact that neurons demand a large amount of energy for their normal functions, decline of the energy production system considerably affects the ability of the nervous systems to function properly. Isolated complex I deficiency is the most common enzyme defect among the groups of OXPHOS abnormality (Bourgeron et al., 1995). Leigh syndrome or Leigh-like diseases are the
Concluding remarks
Recently, fundamental importance of mitochondrial functions has been re-recognized in many aspects (Skulachev, 1999). As described in this review, it is evident that elucidation of complex I function is of significant importance to improve our understanding of life processes. The field of complex I research has been steadily expanding as exemplified by the exponentially increasing number of publications in the last several years. I would like to stress that there are many topics related to
Acknowledgements
I would like to thank Prof. Tomoko Ohnishi for her encouragement and support. I am thankful to Prof. Fevzi Daldal for his critical comments on the manuscript. This is supported by NIH grant (RO1GM30736 to T. Ohnishi).
References (129)
- et al.
Application of the obligate aerobic yeast Yarrowia lipolytica as a eucaryotic model to analyse Leigh syndrome mutations in the complex I core subunits PSST and TYKY
Biochim. Biophys. Acta
(2000) - et al.
Function of conserved acidic residues in the PSST homologue of complex I (NADH: ubiquinone oxidoreductase) from Yarrowia lipolytica
J. Biol. Chem.
(2000) Intimate relationships of the large and the small subunits of all nickel hydrogenases with two nuclear-encoded subunits of mitochondrial NADH: ubiquinone oxidoreductase
Biochim. Biophys. Acta
(1993)- et al.
NADH: ubiquinone oxidoreductase from bovine heart mitochondria. A fourth nuclear encoded subunit with a homologue encoded in chloroplast genomes.
FEBS Lett.
(1992) - et al.
Abnormal RNA processing associated with a novel tRNA mutation in mitochondrial DNA. A potential disease mechanism
J. Biol. Chem.
(1993) Proton-translocation by membrane-bound NADH: ubiquinone-oxidoreductase (complex I) through redox-gated ligand conduction
Biochim. Biophys. Acta
(1997)- et al.
Functional analysis of lymphoblast and cybrid mitochondria containing the 3460, 11778, or 14484 Leber's hereditary optic neuropathy mitochondrial DNA mutation
J. Biol. Chem.
(2000) - et al.
Nitric oxide enhances MPP+ inhibition of complex I
FEBS Lett.
(2001) - et al.
Genetic evidence for the existence of two quinone related inhibitor binding sites in NADH-CoQ reductase
Biochim. Biophys. Acta
(1997) Inhibitors of NADH-ubiquinone reductase: an overview
Biochim. Biophys. Acta
(1998)
Biophysical and structural characterization of proton-translocating NADH-dehydrogenase (complex I) from the strictly aerobic yeast Yarrowia lipolytica
Biochim. Biophys. Acta
A reductant-induced oxidation mechanism for complex I
Biochim. Biophys. Acta
Grim-19, a cell death regulatory gene product, is a subunit of bovine mitochondrial nadh: ubiquinone oxidoreductase (complex I)
J. Biol. Chem.
Conservation of sequences of subunits of mitochondrial complex I and their relationships with other proteins
Biochim. Biophys. Acta
Organization and evolution of structural elements within complex I
Biochim. Biophys. Acta Bioenerg.
A motif for quinone binding sites in respiratory and photosynthetic systems
J. Mol. Biol.
The respiratory complex I of bacteria, archaea and eukarya and its module common with membrane-bound multisubunit hydrogenases
FEBS Lett.
Modular evolution of the respiratory NADH: ubiquinone oxidoreductase and the origin of its modules
J. Theor. Biol.
The site of production of superoxide radical in mitochondrial complex I is not a bound ubisemiquinone but presumably iron–sulfur cluster N2
FEBS Lett.
Three-dimensional structure of bovine NADH: ubiquinone oxidoreductase (complex I) at 22 Å in ice
J. Mol. Biol.
Consistent structure between bacterial and mitochondrial NADH: ubiquinone oxidoreductase (complex I)
J. Mol. Biol.
Three-dimensional structure of NADH-dehydrogenase from Neurospora crassa by electron microscopy and conical tilt reconstruction
J. Mol. Biol.
Reconstitution of the electron transport system I. Preparation and properties of the interacting enzyme complexes
Biochem. Biophys. Res. Commun.
Sequence homologies among mitochondrial DNA-coded URF2, URF4 and URF5
FEBS Lett.
Studies on the electron transfer pathway, topography of iron–sulfur centers, and site of coupling in NADH-Q oxidoreductase
J. Biol. Chem.
Formation and removal of α-synuclei aggregates in cells exposed to mitochondrial inhibitors
J. Biol. Chem.
Quinone specificity of complex I
Biochim. Biophys. Acta
The nuoM arg368his mutation in NADH: ubiquinone oxidoreductase from Rhodobacter capsulatus: a model for the human nd4-11778 mtDNA mutation associated with Leber's hereditary optic neuropathy
Biochim. Biophys. Acta
Electron transfer properties of NADH: ubiquinone reductase in the ND1/3460 and the ND4/11778 mutations of the Leber hereditary optic neuroretinopathy (LHON)
FEBS Lett.
Inhibition of mitochondrial NADH-ubiquinone oxidoreductase activity by 1-methyl-4-phenylpyridinium ion
Biochem. Biophys. Res. Commun.
Characterization of assembly intermediates of NADH: ubiquinone oxidoreductase (complex I) accumulated in Neurospora mitochondria by gene disruption
J. Mol. Biol.
Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenyl-pyridine, a metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine
Life Sci.
Iron–sulfur clusters/semiquinones in complex I
Biochim. Biophys. Acta
Structure–function studies of iron–sulfur clusters and semiquinones in the NADH-Q oxidoreductase segment of the respiratory chain
Biochim. Biophys. Acta
Three classes of inhibitors share a common binding domain in mitochondrial complex I (NADH: ubiquinone oxidoreductase)
J. Biol. Chem.
The mitochondrial DNA mutation ND6*14,484C associated with Leber hereditary optic neuropathy, leads to deficiency of Complex I of the respiratory chain
Biochem. Biophys. Res. Commun.
The nuclear-encoded 18 kDa (IP) AQDQ subunit of bovine heart complex I is phosphorylated by the mitochondrial cAMP-dependent protein kinase
FEBS Lett.
Mutation in the NDUFS4 gene of complex I abolishes cAMP-dependent activation of the complex in a child with fatal neurological syndrome
FEBS Lett.
Evidence for a quinone binding site close to the interface between NUOD and NUOB subunits of complex I
Biochim. Biophys. Acta
Human complex I deficiency: clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect
Biochim. Biophys. Acta
Cryo-electron crystallography of two sub-complexes of bovine complex I reveals the relationship between the membrane and peripheral arms
J. Mol. Biol.
Human complex I defects in neurodegenerative diseases
Biochim. Biophys. Acta
Adenisine triphosphate-dependent reduction of nicotinamide adenine dinucleotide by ferro-cytochrome c in chempsutotrophic bacteria
Nature
Direct interaction between a membrane domain subunit and a connector subunit in the H+-translocating NADH-quinone oxidoreductase
FEBS Lett.
Exploring the membrane domain of the reduced nicotinamide adenine dinucleotide-quinone oxidoreductase of Paracoccus denitrificans: characterization of the NQO7 subunit
Biochemistry
Chronic systemic pesticide exposure reproduces features of Parkinson's disease
Nat. Neurosci.
Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency
Nat. Genet.
Proton translocation in the respiratory chain involving ubiquinone-A hypothetical semiquinone switch mechanism for complex I
Biofactors
Phylogenetic analysis of Leber's hereditary optic neuropathy mitochondrial DNA's indicates multiple independent occurrences of the common mutations
Hum. Mutat.
Mitochondrial DNA complex I and III mutations associated with Leber's hereditary optic neuropathy
Genetics
Cited by (41)
Transcriptome analysis of hepatopancreas and gills of Palaemon gravieri under salinity stress
2023, GeneCitation Excerpt :Therefore, it is not surprising that NDUFs are affected when electron concentrations change due to changes in salinity, as in Sarotherodon melanotheron (Tine et al., 2011). NDUFs are part of the energy production-coupled oxidative phosphorylation system, and their defects might lead to the accumulation of reactive oxygen species (ROS)(Yano, 2002). Thus, it is closely related to oxidative stress.
Pharmacology of ME-344, a novel cytotoxic isoflavone
2019, Advances in Cancer ResearchCitation Excerpt :Complex I (NADH-coenzyme Q oxidoreductase) is the first enzyme complex of the ETC, reducing ubiquinone to ubiquinol by using the electrons donated from the oxidation of NADH from the Krebs cycle (Lenaz, Fato, Baracca, & Genova, 2004). It is also the largest multi-subunit enzyme of the ETC to generate an electrochemical proton gradient by pumping hydrogen ions across the inner mitochondrial membrane, driving ATP production and consequently the efficiency of the OXPHOS process (Holper, Ben-Shachar, & Mann, 2018; Yano, 2002). The impact of ME-344 on mitochondria was investigated by Lim et al., who showed that ME-344 suppresses mitochondrial respiration and complex I activity (and to some extent complex III).
A modeling and simulation perspective on the mechanism and function of respiratory complex I
2018, Biochimica et Biophysica Acta - BioenergeticsUnderstanding mitochondrial complex I assembly in health and disease
2012, Biochimica et Biophysica Acta - BioenergeticsNDUFS4: Creation of a mouse model mimicking a Complex I disorder
2009, Mitochondrion