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Kinetics and control of oxidative phosphorylation in rat liver mitochondria after dexamethasone treatment.
- Source :
-
The Biochemical journal [Biochem J] 2004 Sep 01; Vol. 382 (Pt 2), pp. 491-9. - Publication Year :
- 2004
-
Abstract
- 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.
- Subjects :
- Adenosine Triphosphate biosynthesis
Animals
Body Weight drug effects
Body Weight physiology
Eating physiology
Efficiency drug effects
Efficiency physiology
Fatty Acids, Nonesterified blood
Kinetics
Liver drug effects
Liver physiology
Male
Membrane Potentials drug effects
Membrane Potentials physiology
Organ Size drug effects
Organ Size physiology
Oxidation-Reduction drug effects
Oxygen Consumption drug effects
Oxygen Consumption physiology
Phosphorylation drug effects
Proton Pumps drug effects
Proton Pumps physiology
Protons
Rats
Rats, Sprague-Dawley
Dexamethasone pharmacology
Mitochondria, Liver drug effects
Mitochondria, Liver physiology
Oxidative Phosphorylation drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1470-8728
- Volume :
- 382
- Issue :
- Pt 2
- Database :
- MEDLINE
- Journal :
- The Biochemical journal
- Publication Type :
- Academic Journal
- Accession number :
- 15175015
- Full Text :
- https://doi.org/10.1042/BJ20040696