The specificity of mitochondrial complex I for ubiquinones (original) (raw)
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Journal of Biological Chemistry
NADH-quinone oxidoreductase (complex I) couples electron transfer from NADH to quinone with proton translocation across the membrane. Quinone reduction is a key step for energy transmission from the site of quinone reduction to the remotely located proton-pumping machinery of the enzyme. Although structural biology studies have proposed the existence of a long and narrow quinone-access channel, the physiological relevance of this channel remains debatable. We investigated here whether complex I in bovine heart submitochondrial particles (SMPs) can catalytically reduce a series of oversized ubiquinones (OS-UQs), which are highly unlikely to transit the narrow channel because their side chain includes a bulky “block” that is ~13 Å across. We found that some OS-UQs function as efficient electron acceptors from complex I, accepting electrons with an efficiency comparable to ubiquinone-2. The catalytic reduction and proton translocation coupled with this reduction were completely inhibit...
Biochemistry (Moscow), 2011
NADH:ubiquinone oxidoreductase (complex I) is the most complex component of the mitochondrial respi ratory chain. The major function of the enzyme is oxida tion of the intramitochondrial NADH by ubiquinone (finally by oxygen) thus maintaining the steady state NADH/NAD + ratio, which determines intensity of aero bic oxidative metabolism. Mammalian, yeast, plant, and prokaryotic complex I (NDH 1 homolog) catalyze NADH:quinone oxidoreduction coupled with vectorial proton translocation, thus building up ∆μ Н + needed for ATP synthesis. Mammalian complex I (bovine heart) is composed of 45 different subunits (total molecular mass
Archives of Biochemistry and Biophysics, 2000
Determination of the number of ubiquinone-and inhibitor-binding sites in the mitochondrial complex I (NADH:ubiquinone oxidoreductase) is a controversial question with a direct implication for elaborating a suitable model to explain the bioenergetic mechanism of this complicated enzyme. We have used combinations of both selective inhibitors and common ubiquinone-like substrates to demonstrate the multiplicity of the reaction centers in the complex I in contrast with competition studies that have suggested the existence of a unique binding site for ubiquinone. Our results provide new evidence for the existence of at least two freely exchangeable ubiquinone-binding sites with different specificity for substrates, as well as for a different kinetic interaction of inhibitors with the enzyme.
Biochemical Society Transactions, 1987
Structurc of' uhiquinol : cytochrome c reductase Ubiquinol : cytochrome c reductase (cytochrome reductase) from Neurospora crassa mitochondria is a dimer and the monomeric unit consists of nine different subunits. The subunits I and I I are known as core-proteins, III, IV and V are the cytochromes h, c, and the iron-sulphur protein, and VI to IX are small proteins without prosthetic groups (Weiss & Kolb, 1979). We have recently determined the low-resolution three-dimensional structure of cytochrome reductase and of a bc,-subcomplex of the enzyme by means of electron microscopy of membrane crystals (Leonard ct a/.. 1981; Karlsson et al., 1983). The structure of the dimeric cytochrome reductase shows that the monomeric units are related by a twofold axis running perpendicular to the membrane. They are elongated, protrude 7 nm into the matrix space of mitochondria and 3 nm into the intermembrane space and contact each other partly in the membrane, partly in the matrix space (Figs. 1 and 2). In the structure of the hc,-subcomplex, which is a dimer like the whole enzyme but lacks the core-protein and iron-sulphur protein, the large peripheral section and an outward-facing part of the small peripheral section are missing. Taking into consideration secondary structures of subunits predicted from Abbreviations used: Q. ubiquinone-10; QH2. reduced ubiquinone-10.
Proton pumping of mitochondrial complex I: differential activation by analogs of ubiquinone
Journal of bioenergetics and biomembranes, 1997
As part of the ongoing studies aimed at elucidating the mechanism of the energy conserving function of mitochondrial complex I, NADH: ubiquinone (Q) reductase, we have investigated how short-chain Q analogs activate the proton pumping function of this complex. Using a pH-sensitive fluorescent dye we have monitored both the extent and initial velocity of proton pumping of complex I in submitochondrial particles. The results are consistent with two sites of interaction of Q analogs with complex I, each having different proton pumping capacity. ...
Bioscience, biotechnology, and biochemistry, 2016
We previously produced the unique ubiquinone QT ("decoupling" quinone), the catalytic reduction of which in NADH-quinone oxidoreduction with bovine heart mitochondrial NADH-ubiquinone oxidoreductase (complex I) is completely decoupled from proton translocation across the membrane domain. This feature is markedly distinct from those of typical short-chain quinones such as ubiquinone-1. To further characterize the features of the QT reaction with complex I, we herein synthesized three QT analogs, QT2-QT4, and characterized their electron transfer reactions. We found that all aspects of electron transfer (e.g. electron-accepting activity and membrane potential formation) vary significantly among these analogs. The features of QT2 as decoupling quinone were slightly superior to those of original QT. Based on these results, we conclude that the bound positions of QTs within the quinone binding cavity susceptibly change depending on their side-chain structures, and the positions...
Biochemistry, 2010
NADH-ubiquinone oxidoreductase (Complex I) is located at the entrance of the mitochondrial electron transfer chain and transfers electrons from NADH to ubiquinone with 10 isoprene units (Q 10) coupled with proton pumping. The composition of Complex I, the largest and most complex proton pump in the mitochondrial electron transfer system, especially the contents of Q 10 and phospholipids, has not been well established. An improved purification method including solubilization of mitochondrial membrane with deoxycholate followed by sucrose gradient centrifugation and anion-exchange column chromatography provided reproducibly a heme-free preparation containing 1 Q 10 , 70 phosphorus atoms of phospholipids, 1 zinc ion, 1 FMN, 30 inorganic sulfur ions, and 30 iron atoms as the intrinsic constituents. The rotenonesensitive enzymatic activity of the Complex I preparation was comparable to that of Complex I in the mitochondrial membrane. It has been proposed that Complex I has two Q 10 binding sites, one involved in the proton pump and the other functioning as a converter between one and two electron transfer pathways [