Stimulation of the electron transport chain in mitochondria isolated from rats treated with mannoheptulose or glucagon

Brand, Martin D.; D'Alessandri, Luca; Reis, Helena M. G. P. V.; Hafner, Roderick P.

doi:10.1016/0003-9861(90)90643-d

Cited by 27 publications

(7 citation statements)

References 38 publications

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“…However, it is important not to mix definitions as the values for the coefficients that are obtained will not be comparable. In an earlier study, we concluded that complex IV had no control over respiration in mitochondria respiring on ascorbate plus Ph(NMe,), because the Ph(NMe,), concentration had a (C,) flux control coefficient of approximately one, leaving no residual control for complex IV [24]. This conclusion is wrong using the results of this study; a C, flux control coefficient for Ph(NMe,), of one does not rule out a finite C, or C,] flux control coefficient for complex IV.…”

Section: Discussionmentioning

confidence: 94%

The Sum of Flux Control Coefficients in the Electron‐Transport Chain of Mitochondria

Brand

Vallis

Kesseler

1994

European Journal of Biochemistry

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The sum of the flux control coefficients for group-transfer reactions such as electron transport has been proposed to be two when the coefficients are calculated from experiments in which the concentrations of the electron carriers are changed (C,) but one when they are calculated from changes in the rates of the electron-transfer processes (C,). We tested this proposal using electron transport in uncoupled beef heart, potato tuber and rat liver mitochondria. First, with ascorbate plus N,N,N',N''-tetramethyl-p-phenylenediamine as substrate, the C, flux control coefficients of ascorbate, N,N,N',N''-tetramethyl-p-phenylenediamine, mitochondria and oxygen over electron-transport rate were measured by direct titration of the concentrations of these electron carriers. C , values were close to zero, one, one and zero, respectively, giving a sum of C, flux control coefficients of approximately two. At higher concentrations of N,N,N',N'-tetramethyl-p-phenylenediamine, its C, control decreased and the sum decreased towards one as predicted. Secondly, the C,, control coefficients of groups of electron-transfer processes with succinate or ascorbate plus N,N,N',N'-tetramethyl-p-phenylenediamine as substrate were measured. This was achieved by measuring the effects of KCN (or malonate or N,N,N',N'-tetramethyl-p-phenylenediamine) on system flux when intermediates were allowed to relax and on local flux when intermediates were held constant. The C,, flux control coefficients were calculated as the ratio of the effects on system flux and on local flux. The sum of the C,, flux control coefficients was approximately one. Whether a sum of one or a sum of two was obtained depended entirely on the definition of control coefficients that was used, since either sum was obtained from the same set of data depending on the method of calculation. Both definitions are valid, but they give different information. It is important to be aware of which definition is being used when analysing control coefficients in electron-transport chains and other group-transfer systems.The control of flux through biochemical pathways is shared unequally between all of the participating steps; some steps exert little control whilst others exert more control. Flux control coefficients, CJ, quantify the control exerted by each step over pathway flux [l-31. In the original formulations of Kacser and Burns [3], the flux control coefficient of enzyme E over flux J (Ci) was conveniently defined as the fractional change in pathway flux caused by an infinitesimal fractional change.in the concentration of E as follows:(1) although from the start it was recognised that a definition in terms of control by enzyme activity rather than concentration was in some ways preferable [2, 41.Correspondence to

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Section: Discussionmentioning

confidence: 94%

The Sum of Flux Control Coefficients in the Electron‐Transport Chain of Mitochondria

Brand

Vallis

Kesseler

1994

European Journal of Biochemistry

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“…Under physiological conditions mitochondrial function and thus production is altered by a variety of transient and long-term effectors, e.g. Ca 2+ stimulates NADH delivery to the electron transport chain (Denton & McCormack, 1985); nitric oxide (Cooper, 2002) or phosphorylation (Lee et al ., 2002a) modulates complex IV; oxidized glutathione inhibits reversibly complex I and α -ketglutarate dehydrogenase (Nulton-Persson et al ., 2003) to slow TCA cycle activity; glucagon stimulates complex II (Brand et al ., 1990), thyroxine modulates proton leak (Harper & Brand, 1993); and part of the anti-aging effect of calorie-restricted (CR) diets is to cause lowering of ∆µ H + , and thus production, by increasing proton leak and decreasing substrate oxidation. Insulin reverses these effects (Lambert & Merry, 2003).…”

Section: The Electron Transport Chainmentioning

confidence: 99%

Is defective electron transport at the hub of aging?

Maklashina

Ackrell

2003

Aging Cell

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SummaryThe bulwark of the mitochondrial theory of aging is that a defective respiratory chain initiates the death cascade. The increased production of superoxide is suggested to result in progressive oxidant damage to cellular components and particularly to mtDNA that encodes subunits assembled in respiratory complexes. Earlier studies of respiration in muscle mitochondria obtained from large cohorts of patients supported this notion by showing that either singly or in combinations, the respiratory complexes exhibited decreased activity in the elderly. The following critique of the most cited publications over the past decade points out the systematic errors that put earlier work at odds with recent findings. These later investigations indicate that aging has no overt effect on either the electron transport system or oxidative phosphorylation.

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“…An alternative interpretation is that the force driving proton leak, the mitochondrial membrane potential (⌬ m ), is reduced during hibernation, and therefore decreased state 4 respiration may be a consequence of upstream metabolic control. Mechanistically, this can be achieved by decreasing the activity of the enzymes responsible for generating the ⌬ m , including substrate translocases, dehydrogenases, and enzymes of the respiratory chain (7). Distinguishing which of these alternatives is responsible for metabolic depression requires parallel measurement of oxygen consumption ⌬ m and may have important implications for the evolutionary conservation of metabolic depression across a wide array of species.…”

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confidence: 99%

Tissue-specific depression of mitochondrial proton leak and substrate oxidation in hibernating arctic ground squirrels

Barger

Brand

Barnes

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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A significant proportion of standard metabolic rate is devoted to driving mitochondrial proton leak, and this futile cycle may be a site of metabolic control during hibernation. To determine if the proton leak pathway is decreased during metabolic depression related to hibernation, mitochondria were isolated from liver and skeletal muscle of nonhibernating (active) and hibernating arctic ground squirrels (Spermophilus parryii). At an assay temperature of 37 degrees C, state 3 and state 4 respiration rates and state 4 membrane potential were significantly depressed in liver mitochondria isolated from hibernators. In contrast, state 3 and state 4 respiration rates and membrane potentials were unchanged during hibernation in skeletal muscle mitochondria. The decrease in oxygen consumption of liver mitochondria was achieved by reduced activity of the set of reactions generating the proton gradient but not by a lowered proton permeability. These results suggest that mitochondrial proton conductance is unchanged during hibernation and that the reduced metabolism in hibernators is a partial consequence of tissue-specific depression of substrate oxidation.

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Stimulation of the electron transport chain in mitochondria isolated from rats treated with mannoheptulose or glucagon

Cited by 27 publications

References 38 publications

The Sum of Flux Control Coefficients in the Electron‐Transport Chain of Mitochondria

The Sum of Flux Control Coefficients in the Electron‐Transport Chain of Mitochondria

Is defective electron transport at the hub of aging?

Tissue-specific depression of mitochondrial proton leak and substrate oxidation in hibernating arctic ground squirrels

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