Complex I, NADH:quinone oxidoreductase, EC1.6.5.3, is the first enzyme of the respiratory chain and thus a central player in the energy production of the cell. [1] Energy production involves the transfer of electrons from substrate to ATP and NADH, and Complex I is the main entry-point for electrons into the electron-transport chain. [2] [3] [4] Complex I catalyzes the reversible oxidation of NADH by transferring two electrons to ubiquinone and translocating four protons across the eukaryotic inner mitochondrial membrane or the bacterial cytoplasmic membrane; it achieves this at the rate of 200 catalytic-cycles per second. [5] NADH:quinone oxidoreductase thus effectively pumps protons across these membranes. [6]
Human complex I is involved in numerous
pathological conditions and
degenerative processes. With 14 central and up to 32 accessory
subunits, complex I is among the largest membrane-bound protein
assemblies.
Human mitochondrial complex I has a total
molecular weight of close to
1 MDa, and the bacterial protein-assembly weighs in at nearly 550 kDa.
The composition of the complex varies between species, with bacteria having the minimal model number, of 14 subunits, none of which can be removed without compromising function. This suggests that all complexes I share a common mechanism. In all organisms studied these 14 core subunits form into a characteristic L-shape, [7] with the peripheral arm of the L protruding into the bacterial cytoplasm/mitochondrial matrix and the other embedded in the membrane, the mass of the whole being more-or-less equally distributed between the two arms, each of which is, including the junction, approximately 180 Angstrom in length. The eukaryotic and hence human complex I consists of more than 40 individual subunits - the 14 core subunits and an additional 26 accessory subunits. There are functional differences between the bacterial and the mitochondrial enzymes, such as the vertebrate complex showing a deactive-to-active state transition on addition of substrates that is not shown by bacterial and many non-vertebrate complex Is. [8] [9] The transition is shown by Yarrowia lipolytica and the transition is much faster rate than in the bovine complex I. [10] Many of the subunits are equivalent between bovine and Y.lipolytica complex I there are at least three fungal-specific subunits in the Y.lipolytica enzyme, and up to 10 mammalian-specific accessory subunits present in Bos taurus with no counterpart in Y.lipolytica. [7]
Complex I has evolved by addition of accessory subunits, up to 31 in the human mitochondrial complex. The gamma-proteobacteria Escherichia coli and the Deinococci Thermus thermophilus have only the core 14 in their complex I. It was initially understood that all additional subunits arose only in the eukaryotic lineage, however the alpha-proteobacteria Paracoccus denitrificans, considered to be closely related to the ancient symbiont of eukaryotes, is found to carry up to three of the "mitochondrial" accessory subunits, NDUFA12, NDUFS4 and 13kDa (subsequently found to be a short zinc-finger protein in Pfam). [11] This suggests that the complex was evolving through the addition of accessory subunits before the original endosymbiotic event that led to the creation of the eukaryotic cell. [11] Based on the the homologies between bacterial and mammalian enzymes it has been postulated that the complex originated from the fusion of distinct pre-existing protein assemblies that have over time combined their activities into one complex. [12]The hydrogenase has evolved from the the small and large subbunits of the bacterial nickel-hydrogenases that are conserved in subunit NDUFS7 and NDUFS2. [13]The hydrogenase has acquired a ferredoxin, ND4, a membrane-bound quinone-reduction site, ND1, a transport protein, ND4 and a protein of unknown function, NDUFS3; further bacterial evolution added to the transporter module, or antiporter module ND5 and ND2 as well as ND3, ND6 and ND4L. [14]Finally the dehydrogenase-unit made up of NDUFS1 and NDUFV1-V2. [15]
Table ref below: Celegans and human and Ecoli [16] Arabidopsis and rice: [17]
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Complex I, NADH:quinone oxidoreductase, EC1.6.5.3, is the first enzyme of the respiratory chain and thus a central player in the energy production of the cell. [1] Energy production involves the transfer of electrons from substrate to ATP and NADH, and Complex I is the main entry-point for electrons into the electron-transport chain. [2] [3] [4] Complex I catalyzes the reversible oxidation of NADH by transferring two electrons to ubiquinone and translocating four protons across the eukaryotic inner mitochondrial membrane or the bacterial cytoplasmic membrane; it achieves this at the rate of 200 catalytic-cycles per second. [5] NADH:quinone oxidoreductase thus effectively pumps protons across these membranes. [6]
Human complex I is involved in numerous
pathological conditions and
degenerative processes. With 14 central and up to 32 accessory
subunits, complex I is among the largest membrane-bound protein
assemblies.
Human mitochondrial complex I has a total
molecular weight of close to
1 MDa, and the bacterial protein-assembly weighs in at nearly 550 kDa.
The composition of the complex varies between species, with bacteria having the minimal model number, of 14 subunits, none of which can be removed without compromising function. This suggests that all complexes I share a common mechanism. In all organisms studied these 14 core subunits form into a characteristic L-shape, [7] with the peripheral arm of the L protruding into the bacterial cytoplasm/mitochondrial matrix and the other embedded in the membrane, the mass of the whole being more-or-less equally distributed between the two arms, each of which is, including the junction, approximately 180 Angstrom in length. The eukaryotic and hence human complex I consists of more than 40 individual subunits - the 14 core subunits and an additional 26 accessory subunits. There are functional differences between the bacterial and the mitochondrial enzymes, such as the vertebrate complex showing a deactive-to-active state transition on addition of substrates that is not shown by bacterial and many non-vertebrate complex Is. [8] [9] The transition is shown by Yarrowia lipolytica and the transition is much faster rate than in the bovine complex I. [10] Many of the subunits are equivalent between bovine and Y.lipolytica complex I there are at least three fungal-specific subunits in the Y.lipolytica enzyme, and up to 10 mammalian-specific accessory subunits present in Bos taurus with no counterpart in Y.lipolytica. [7]
Complex I has evolved by addition of accessory subunits, up to 31 in the human mitochondrial complex. The gamma-proteobacteria Escherichia coli and the Deinococci Thermus thermophilus have only the core 14 in their complex I. It was initially understood that all additional subunits arose only in the eukaryotic lineage, however the alpha-proteobacteria Paracoccus denitrificans, considered to be closely related to the ancient symbiont of eukaryotes, is found to carry up to three of the "mitochondrial" accessory subunits, NDUFA12, NDUFS4 and 13kDa (subsequently found to be a short zinc-finger protein in Pfam). [11] This suggests that the complex was evolving through the addition of accessory subunits before the original endosymbiotic event that led to the creation of the eukaryotic cell. [11] Based on the the homologies between bacterial and mammalian enzymes it has been postulated that the complex originated from the fusion of distinct pre-existing protein assemblies that have over time combined their activities into one complex. [12]The hydrogenase has evolved from the the small and large subbunits of the bacterial nickel-hydrogenases that are conserved in subunit NDUFS7 and NDUFS2. [13]The hydrogenase has acquired a ferredoxin, ND4, a membrane-bound quinone-reduction site, ND1, a transport protein, ND4 and a protein of unknown function, NDUFS3; further bacterial evolution added to the transporter module, or antiporter module ND5 and ND2 as well as ND3, ND6 and ND4L. [14]Finally the dehydrogenase-unit made up of NDUFS1 and NDUFV1-V2. [15]
Table ref below: Celegans and human and Ecoli [16] Arabidopsis and rice: [17]
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