The present investigation was undertaken in order to evaluate the contributions of ATP synthesis and proton leak reactions to the rate of active respiration of liver mitochondria, which is altered following dexamethasone treatment (1.5 mg/kg per day for 5 days). We applied top-down metabolic control analysis and its extension, elasticity analysis, to gain insight into the mechanisms of glucocorticoid regulation of mitochondrial bioenergetics. Liver mitochondria were isolated from dexamethasone-treated, pair-fed and control rats when in a fed or overnight fasted state. Injection of dexamethasone for 5 days resulted in an increase in the fraction of the proton cycle of phosphorylating liver mitochondria, which was associated with a decrease in the efficiency of the mitochondrial oxidative phosphorylation process in liver. This increase in proton leak activity occurred with little change in the mitochondrial membrane potential, despite a significant decrease in the rate of oxidative phosphorylation. Regulation analysis indicates that mitochondrial membrane potential homoeostasis is achieved by equal inhibition of the mitochondrial substrate oxidation and phosphorylation reactions in rats given dexamethasone. Our results also suggest that active liver mitochondria from dexamethasone-treated rats are capable of maintaining phosphorylation flux for cellular purposes, despite an increase in the energetic cost of mitochondrial ATP production due to increased basal proton permeability of the inner membrane. They also provide a complete description of the effects of dexamethasone treatment on liver mitochondrial bioenergetics.
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Research Article|
August 24 2004
Kinetics and control of oxidative phosphorylation in rat liver mitochondria after dexamethasone treatment
Damien ROUSSEL;
Damien ROUSSEL
1
1Laboratoire de Biochimie et Biologie Moléculaire, INSERM EMI-U 00.18, 4 rue Larrey, F-49033 Angers cedex, France
1To whom correspondence should be addressed (email damroussel@yahoo.fr).
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Jean-François DUMAS;
Jean-François DUMAS
1Laboratoire de Biochimie et Biologie Moléculaire, INSERM EMI-U 00.18, 4 rue Larrey, F-49033 Angers cedex, France
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Gilles SIMARD;
Gilles SIMARD
1Laboratoire de Biochimie et Biologie Moléculaire, INSERM EMI-U 00.18, 4 rue Larrey, F-49033 Angers cedex, France
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Yves MALTHIÈRY;
Yves MALTHIÈRY
1Laboratoire de Biochimie et Biologie Moléculaire, INSERM EMI-U 00.18, 4 rue Larrey, F-49033 Angers cedex, France
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Patrick RITZ
Patrick RITZ
1Laboratoire de Biochimie et Biologie Moléculaire, INSERM EMI-U 00.18, 4 rue Larrey, F-49033 Angers cedex, France
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Publisher: Portland Press Ltd
Received:
April 28 2004
Revision Received:
May 25 2004
Accepted:
June 03 2004
Accepted Manuscript online:
June 03 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2004
Biochem J (2004) 382 (2): 491–499.
Article history
Received:
April 28 2004
Revision Received:
May 25 2004
Accepted:
June 03 2004
Accepted Manuscript online:
June 03 2004
Citation
Damien ROUSSEL, Jean-François DUMAS, Gilles SIMARD, Yves MALTHIÈRY, Patrick RITZ; Kinetics and control of oxidative phosphorylation in rat liver mitochondria after dexamethasone treatment. Biochem J 1 September 2004; 382 (2): 491–499. doi: https://doi.org/10.1042/BJ20040696
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