The Mitochondrial Complex I: Progress in Understanding of Catalytic Properties

Vinogradov, Andrei D.; Grivennikova, Vera G.

doi:10.1080/15216540152845920

Cited by 64 publications

(50 citation statements)

References 39 publications

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“…It was suggested that progressive impairment of several components of the mitochondrial function measured in permeabilised heart muscle fibres, such as oxidative phosphorylation (OXPHOS, respiratory state III), ATP production efficiency and the capacity of single complexes of the Electron Transport System (ETS) shape the temperature of heart failure (T HF ). High temperature changes the fluidity of mitochondrial membranes, which can entail increased proton leak through the inner membrane ([19] for review), resulting in decreased coupling ratios and causing decreased membrane potential [34, 35] and, as a consequence, inhibit the electrogenic transport of substrates, i. e. the transport of charged substrates like glutamate and malate that leads to the translocation of net charge across the membrane [36]. This indicates that mitochondrial metabolism is involved in functional constraints and thermal limitation of this tissue [28, 29, 32, 33].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial acclimation potential to ocean acidification and warming of Polar cod (Boreogadus saida) and Atlantic cod (Gadus morhua)

et al. 2017

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BackgroundOcean acidification and warming are happening fast in the Arctic but little is known about the effects of ocean acidification and warming on the physiological performance and survival of Arctic fish.ResultsIn this study we investigated the metabolic background of performance through analyses of cardiac mitochondrial function in response to control and elevated water temperatures and PCO2 of two gadoid fish species, Polar cod (Boreogadus saida), an endemic Arctic species, and Atlantic cod (Gadus morhua), which is a temperate to cold eurytherm and currently expanding into Arctic waters in the wake of ocean warming. We studied their responses to the above-mentioned drivers and their acclimation potential through analysing the cardiac mitochondrial function in permeabilised cardiac muscle fibres after 4 months of incubation at different temperatures (Polar cod: 0, 3, 6, 8 °C and Atlantic cod: 3, 8, 12, 16 °C), combined with exposure to present (400μatm) and year 2100 (1170μatm) levels of CO2.OXPHOS, proton leak and ATP production efficiency in Polar cod were similar in the groups acclimated at 400μatm and 1170μatm of CO2, while incubation at 8 °C evoked increased proton leak resulting in decreased ATP production efficiency and decreased Complex IV capacity. In contrast, OXPHOS of Atlantic cod increased with temperature without compromising the ATP production efficiency, whereas the combination of high temperature and high PCO2 depressed OXPHOS and ATP production efficiency.ConclusionsPolar cod mitochondrial efficiency decreased at 8 °C while Atlantic cod mitochondria were more resilient to elevated temperature; however, this resilience was constrained by high PCO2. In line with its lower habitat temperature and higher degree of stenothermy, Polar cod has a lower acclimation potential to warming than Atlantic cod.

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Section: Introductionmentioning

confidence: 99%

Mitochondrial acclimation potential to ocean acidification and warming of Polar cod (Boreogadus saida) and Atlantic cod (Gadus morhua)

et al. 2017

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“…Despite advanced biochemical analysis of the kinetic behavior of both forms of complex I (20), the functional role of the observed heterogeneity has not yet been explained. We have now investigated the effect of nitrosothiols and ONOO Ϫ on the A-and D-forms of the enzyme.…”

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confidence: 99%

“…Two catalytically and structurally distinct forms exist in any given preparation of the enzyme as follows: one is the fully competent, so-called "active" A-form and the other is the disabled, silent, "de-activated" D-form. Socalled pseudoreversible A/D transitions have been described in mammalian complex I (18) and other eukaryotic complex I (19) and have been reviewed in detail (17,20). After exposure of idle enzyme preparations (mitochondria (21), submitochondrial particles (SMP) (18), or purified complex I (22)) to elevated but physiological temperatures (Ͼ30°C) in the absence of substrate, when catalytic turnover cannot occur, the enzyme converts to the D-form.…”

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confidence: 99%

S-Nitrosation of Mitochondrial Complex I Depends on Its Structural Conformation

Galkin

Moncada

2007

Journal of Biological Chemistry

115

114

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Proton-translocating NADH:ubiquinone oxidoreductase (EC 1.6.5.3, complex I or type I NADH dehydrogenase) is the most complex enzyme of the mitochondrial respiratory chain. It is responsible for oxidation of matrix NADH and is the major entry point for electrons to the respiratory chain. Mammalian complex I consists of at least 45 subunits (1), of which more than 30 are so-called "accessory" subunits, not directly involved in catalysis, whose functions are still unclear. Some of them may have a structural role, assisting in the assembly of the enzyme (2), whereas others may be necessary for the fine regulation of the activity of the enzyme in response to signals from the cytoplasm and matrix.Some years ago inhibition of complex I-mediated respiration was demonstrated in cells after incubation with activated macrophages (3). Following the discovery that nitric oxide (NO) 2 is generated endogenously and acts as a biological mediator (4), this inhibition of complex I activity was found to be due to NO (5). An inhibitory effect of the combined action of NO and superoxide anion on complexes I and II was demonstrated in preparations of intact mitochondria. This was shown to be due to peroxynitrite (ONOO Ϫ ), a compound that explains the NOdependent inactivation of several components of the respiratory chain (6 -8). Our group found that prolonged exposure to high concentrations of NO led to persistent inhibition of complex I, which we attributed to nitrosation of critical thiol residue(s) (9 -11), a finding that has been confirmed by other groups (12-16). Although the degree of inhibition of complex 1 caused by various NO donors and the stoichiometry of the subsequent modification(s) have been investigated, the precise nature of the targeted subunit(s) and the possibility of nitrosation of complex I during physiological processes have not been established.The catalytic properties of eukaryotic complex I are not simple (for a review see Ref. 17). Two catalytically and structurally distinct forms exist in any given preparation of the enzyme as follows: one is the fully competent, so-called "active" A-form and the other is the disabled, silent, "de-activated" D-form. Socalled pseudoreversible A/D transitions have been described in mammalian complex I (18) and other eukaryotic complex I (19) and have been reviewed in detail (17,20). After exposure of idle enzyme preparations (mitochondria (21), submitochondrial particles (SMP) (18), or purified complex I (22)) to elevated but physiological temperatures (Ͼ30°C) in the absence of substrate, when catalytic turnover cannot occur, the enzyme converts to the D-form. In such a preparation there is a considerable lag phase during the continuous assay of the NADH: ubiquinone oxidoreductase reaction. Addition of a small (5-10 M) pulse of NADH before the assay results in activation of the enzyme after several slow turnovers when NADH is oxidized by the quinone. This eliminates the lag phase, and the enzyme becomes fully active and catalyzes oxidation of NADH at a linear rate (18,22)...

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“…Maintenance of the fraction of complex I in the D-form would allow fast responses to changes in conditions such as a reductive pressure, ATP demand and oxygen availability by analogy with the well-known phenomenon of excess capacity of cytochrome c oxidase [44–46]. Therefore the A/D transition could be one of the mechanisms for fine-tuning enzyme activity in different tissues [5,18,47,48]. The time course of complex I deactivation after cardiac arrest reveals a much higher A/D transition rate in brain compared with heart tissue (Figure 2) and might explain the greater vulnerability of complex brain functions to oxygen deprivation.…”

Section: Physiological Effect Of the A/d Transitionmentioning

confidence: 99%

Molecular mechanism and physiological role of active–deactive transition of mitochondrial complex I

Babot

Galkin

2013

Biochemical Society Transactions

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The unique feature of mitochondrial complex I is the so-called A/D transition (active–deactive transition). The A-form catalyses rapid oxidation of NADH by ubiquinone (k ~104 min−1) and spontaneously converts into the D-form if the enzyme is idle at physiological temperatures. Such deactivation occurs in vitro in the absence of substrates or in vivo during ischaemia, when the ubiquinone pool is reduced. The D-form can undergo reactivation given both NADH and ubiquinone availability during slow (k ~1–10 min−1) catalytic turnover(s). We examined known conformational differences between the two forms and suggested a mechanism exerting A/D transition of the enzyme. In addition, we discuss the physiological role of maintaining the enzyme in the D-form during the ischaemic period. Accumulation of the D-form of the enzyme would prevent reverse electron transfer from ubiquinol to FMN which could lead to superoxide anion generation. Deactivation would also decrease the initial burst of respiration after oxygen reintroduction. Therefore the A/D transition could be an intrinsic protective mechanism for lessening oxidative damage during the early phase of reoxygenation. Exposure of Cys39 of mitochondrially encoded subunit ND3 makes the D-form susceptible for modification by reactive oxygen species and nitric oxide metabolites which arrests the reactivation of the D-form and inhibits the enzyme. The nature of thiol modification defines deactivation reversibility, the reactivation timescale, the status of mitochondrial bioenergetics and therefore the degree of recovery of the ischaemic tissues after reoxygenation.

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The Mitochondrial Complex I: Progress in Understanding of Catalytic Properties

Cited by 64 publications

References 39 publications

Mitochondrial acclimation potential to ocean acidification and warming of Polar cod (Boreogadus saida) and Atlantic cod (Gadus morhua)

Mitochondrial acclimation potential to ocean acidification and warming of Polar cod (Boreogadus saida) and Atlantic cod (Gadus morhua)

S-Nitrosation of Mitochondrial Complex I Depends on Its Structural Conformation

Molecular mechanism and physiological role of active–deactive transition of mitochondrial complex I

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