scholarly journals Effects of thyroid hormone on mitochondrial oxidative phosphorylation

1985 ◽  
Vol 226 (1) ◽  
pp. 183-192 ◽  
Author(s):  
A J Verhoeven ◽  
P Kamer ◽  
A K Groen ◽  
J M Tager
Keyword(s):  
Thyroid Hormone ◽  
Oxidative Phosphorylation ◽  
Adenine Nucleotide ◽  
Hormone Treatment ◽  
Adenine Nucleotide Translocator ◽  
Control Coefficient ◽  
Bc1 Complex ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Flux Control ◽  
Flux Control Coefficient

In order to locate sites of action of thyroid hormone on mitochondrial oxidative phosphorylation we have used an experimental application of control analysis as previously described [Groen, Wanders, Westerhoff, Van der Meer & Tager (1982) J. Biol. Chem. 257, 2754-2757]. Rat-liver mitochondria were isolated from hypothyroid rats or from hypothyroid rats 24 h after treatment with a single dose of 3,3′,5-triiodothyronine (T3). The amount of control exerted by four different steps on State-3 respiration with succinate as respiratory substrate was quantified by using specific inhibitors. The hormone treatment resulted in an increase in the flux control coefficient of the adenine nucleotide translocator, the dicarboxylate carrier and cytochrome c oxidase and a decrease in the flux control coefficient of the bc1-complex. The results of this analysis indicate that thyroid hormone treatment results in an activation of the bc1-complex and of at least one other enzyme, possibly succinate dehydrogenase. Measurement of the extramitochondrial ATP/ADP ratio at different rates of respiration (induced by addition of different amounts of hexokinase in the presence of glucose and ATP) showed that the adenine nucleotide translocator operates at a higher (ATP/ADP)out after T3 treatment, which supports previous reports on stimulation of this step by thyroid hormone.

scholarly journals Alteration of mitochondrial oxidative phosphorylation in aged skeletal muscle involves modification of adenine nucleotide translocator

2010 ◽  
Vol 1797 (2) ◽  
pp. 143-151 ◽  
Author(s):  
Gilles Gouspillou ◽  
Isabelle Bourdel-Marchasson ◽  
Richard Rouland ◽  
Guillaume Calmettes ◽  
Jean-Michel Franconi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Oxidative Phosphorylation ◽  
Adenine Nucleotide ◽  
Adenine Nucleotide Translocator ◽  
Mitochondrial Oxidative Phosphorylation

scholarly journals Thyroid-hormone control of state-3 respiration in isolated rat liver mitochondria

1990 ◽  
Vol 265 (3) ◽  
pp. 731-734 ◽  
Author(s):  
R P Hafner ◽  
G C Brown ◽  
M D Brand
Keyword(s):  
Thyroid Hormone ◽  
Atp Synthase ◽  
Adenine Nucleotide ◽  
Liver Mitochondria ◽  
Proton Leak ◽  
Rat Liver Mitochondria ◽  
Protonmotive Force ◽  
Adenine Nucleotide Translocator ◽  
Hormone Control ◽  
Kinetics Of

Oxidative phosphorylation can be treated as two groups of reactions; those that generate protonmotive force (dicarboxylate carrier, succinate dehydrogenase and the respiratory chain) and those that consume protonmotive force (adenine nucleotide and phosphate carriers. ATP synthase and proton leak). Mitochondria from hypothyroid rats have lower rates of respiration in the presence of ADP (state 3) than euthyroid controls. We show that the kinetics of the protonmotive-force generators are unchanged in mitochondria from hypothyroid animals, but the kinetics of the protonmotive-force consumers are altered, supporting proposals that the important effects of thyroid hormone on state 3 are on the ATP synthase or the adenine nucleotide translocator.

scholarly journals Evidence that the flux control coefficient of the respiratory chain is high during gluconeogenesis from lactate in hepatocytes from starved rats. Implications for the hormonal control of gluconeogenesis and action of hypoglycaemic agents

1987 ◽  
Vol 247 (2) ◽  
pp. 449-457 ◽  
Author(s):  
H J Pryor ◽  
J E Smyth ◽  
P T Quinlan ◽  
A P Halestrap
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Respiratory Chain ◽  
Glucose Production ◽  
Hormonal Control ◽  
Acid Oxidation ◽  
Control Coefficient ◽  
Atp Content ◽  
Flux Control ◽  
Flux Control Coefficient

1. Increasing concentrations of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), a mild respiratory-chain inhibitor [Halestrap (1987) Biochim. Biophys. Acta 927, 280-290], caused progressive inhibition of glucose production from lactate + pyruvate by hepatocytes from starved rats incubated in the presence or absence of oleate and gluconeogenic hormones. 2. No significant changes in tissue ATP content were observed, but there were concomitant decreases in ketone-body output and cytochrome c reduction and increases in NADH fluorescence and the ratios of [lactate]/[pyruvate] and [beta-hydroxybutyrate]/[acetoacetate]. 3. The inhibition by DCMU of palmitoylcarnitine oxidation by isolated liver mitochondria was used to calculate a flux control coefficient of the respiratory chain towards gluconeogenesis. In the presence of 1 mM-oleate, the calculated values were 0.61, 0.39 and 0.25 in the absence of hormone and in the presence of glucagon or phenylephrine respectively, consistent with activation of the respiratory chain in situ as previously suggested [Quinlan & Halestrap (1986) Biochem. J. 236, 789-800]. 4. Cytoplasmic oxaloacetate concentrations were shown to decrease under these conditions, implying inhibition of pyruvate carboxylase. 5. Inhibition of gluconeogenesis from fructose and dihydroxyacetone was also observed with DCMU and was accompanied by an increased output of lactate + pyruvate, suggesting that activation of pyruvate kinase was occurring. With the latter substrate, measurements of tissue ADP and ATP contents showed that DCMU caused a small fall in [ATP]/[ADP] ratio. 6. Two inhibitors of fatty acid oxidation, pent-4-enoate and 2-tetradecylglycidate, were shown to abolish and to decrease respectively the effects of hormones, but not valinomycin, on gluconeogenesis from lactate + pyruvate, without changing tissue ATP content. 7. It is concluded that the hormonal increase in mitochondrial matrix volume stimulates fatty acid oxidation and respiratory-chain activity, allowing stimulation of pyruvate carboxylation and thus gluconeogenesis to occur without major changes in [ATP]/[ADP] or [NADH]/[NAD+] ratios. 8. The high flux control coefficient of the respiratory chain towards gluconeogenesis may account for the hypoglycaemic effect of mild respiratory-chain inhibitors.

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