Complex I oxidises NADH to NAD+, reduces CoQ to QH2

Stable Identifier
Reaction [transition]
Homo sapiens
NADH enters the respiratory chain at Complex I
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Complex I (NADH:ubiquinone oxidoreductase or NADH dehydrogenase) utilizes NADH formed from glycolysis and the TCA cycle to pump protons out of the mitochondrial matrix. It is the largest enzyme complex in the electron transport chain, containing 45 subunits. Seven subunits (ND1-6, ND4L) are encoded by mitochondrial DNA (Loeffen et al [1998]), the remainder are encoded in the nucleus. The enzyme has a FMN prosthetic group and 8 Iron-Sulfur (Fe-S) clusters. The electrons from NADH oxidation pass through the flavin (FMN) and Fe-S clusters to ubiquinone (CoQ). This electron transfer is coupled with the translocation of protons from the mitochondrial matrix to the intermembrane space. For each electron transferred, 2 protons can be pumped out of the matrix. As there are 2 electrons transferred, 4 protons can be pumped out.
Complex I is made up of 3 sub-complexes - Iron-Sulfur protein fraction (IP), Flavoprotein fraction (FP) and the Hydrophobic protein fraction (HP), probably arranged in an L-shaped structure with the IP and FP fractions protruding into the mitochondrial matrix and the HP arm lying within the inner mitochondrial membrane. The overall reaction can be summed as below:
NADH + Ubiquinone + 5H+ (mito. matrix) = NAD+ + Ubiquinol + 4H+ (intermemb. space)
The electrons from complex I are transferred to ubiquinone (Coenzyme Q, CoQ), a small mobile carrier of electrons located within the inner membrane. Ubiquinone is reduced to ubiquinol (QH2) during this process.

Mitochondrial coenzyme Q-binding protein COQ10 homologs A and B (COQ10A and B) are thought to be required for correct coenzyme CoQ in the respiratory chain. Their function in humans is unknown but the yeast model suggests functions in facilitating de novo CoQ biosynthesis and in delivering it to one or more complexes of the respiratory electron transport chain (Barros et al. 2005, Allan et al. 2013).

Literature References
PubMed ID Title Journal Year
11695836 Human NADH:ubiquinone oxidoreductase

Smeitink, J, Sengers, R, Trijbels, F, van den Heuvel, L

J Bioenerg Biomembr 2001
12837546 The nuclear encoded subunits of complex I from bovine heart mitochondria

Hirst, J, Fearnley, IM, Carroll, J, Shannon, RJ, Walker, JE

Biochim Biophys Acta 2003
12231006 The energy-transducing NADH: quinone oxidoreductase, complex I

Yano, T

Mol Aspects Med 2002
23270816 A conserved START domain coenzyme Q-binding polypeptide is required for efficient Q biosynthesis, respiratory electron transport, and antioxidant function in Saccharomyces cerevisiae

Hill, S, Loo, JA, Liau, WS, Hirano, K, Allan, CM, Shepherd, JN, Morvaridi, S, Johnson, JS, Ji, Z, Clarke, CF, Saiki, R, Kawashima, T

Biochim. Biophys. Acta 2013
14741580 The gross structure of the respiratory complex I: a Lego System

Friedrich, T, Bottcher, B

Biochim Biophys Acta 2004
16230336 The Saccharomyces cerevisiae COQ10 gene encodes a START domain protein required for function of coenzyme Q in respiration

Johnson, A, Gin, P, Barros, MH, Marbois, BN, Tzagoloff, A, Clarke, CF

J. Biol. Chem. 2005
15250827 Structural organization of mitochondrial human complex I: role of the ND4

Mousson de Camaret, B, Hofhaus, G, Ramus, C, Bourges, I, Remacle, C, Issartel, JP, Cardol, P, Beugnot, R

Biochem J 2004
9878551 cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase:

Smeitink, JA, Loeffen, JL, Schuelke, M, Triepels, RH, Smeets, RJ, Buskens, CA, van den Heuvel, LP, Trijbels, JM

Biochem Biophys Res Commun 1998
Event Information
Catalyst Activity

NADH dehydrogenase (ubiquinone) activity of Complex I [mitochondrial inner membrane]

This event is regulated
Orthologous Events
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