Decrease in mitochondrial energy coupling by thyroid hormones: a physiological effect rather than a pathological hyperthyroidism consequence

Bobyleva, Valentina; Pazienza, Teresa Loredana; Maseroli, R; Tomasi, Aldo; Salvioli, Stefano; Cossarizza, Andrea; Franceschi, Claudio; Skulachev, Vladimir P.

doi:10.1016/s0014-5793(98)00700-5

Cited by 41 publications

(17 citation statements)

References 47 publications

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“…The small but reproducible recoupling effects of cAtr and albumin on the control mitochondria in the absence of any added uncouplers is consistent with the assumption that normally the mitochondrial energy coupling is not maximal. This observation is in line with a recent finding by Bobyleva et al [19]that mitochondrial membrane potential in the intact rat liver cells of the euthyroid rats appears to be somewhat lower than maximal level observed in the hypothyroid animals. Such a ‘mild uncoupling’ inherent in normal mitochondria may be essential to prevent the O −⋅ 2 production in the respiratory chain [17, 20, 21].…”

Section: Discussionsupporting

confidence: 93%

Thermoregulatory uncoupling in heart muscle mitochondria: involvement of the ATP/ADP antiporter and uncoupling protein

Simonyan

Skulachev

1998

FEBS Letters

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Possible involvement of the ATP/ADP antiporter and uncoupling protein (UCP) in thermoregulatory uncoupling of oxidative phosphorylation in heart muscle has been studied. To this end, effects of carboxyatractylate (cAtr) and GDP, specific inhibitors of the antiporter and UCP, on the membrane potential of the oligomycin-treated mitochondria from cold-exposed (6³C, 48 h) and control rats have been measured. It is found that cAtr increases the membrane potential level in both cold-exposed and non-exposed groups, the effect being strongly enhanced by cooling. As for GDP, it is effective only in mitochondria from the cold-exposed rats. In these mitochondria, the coupling effect of GDP is smaller than that of cAtr. CDP, which does not interact with UCP, is without any influence on membrane potential. The cold exposure is found to increase the uncoupling efficiency of added natural (palmitate) or artificial (SF6847) uncouplers, the increase being cAtr-and GDP-sensitive in the case of palmitate. The fatty acid-free bovine serum albumin enhances v v8 8 in both cold-exposed and control groups, the effect being much larger in the former case. It is concluded that in heart muscle mitochondria the ATP/ADP antiporter is responsible for the`mild uncoupling' under normal conditions and for major portion of the thermoregulatory uncoupling in the cold whereas the rest of thermoregulatory uncoupling is served by UCP (presumably by UCP2 since the UCP2 mRNA level is shown to strongly increase in rat heart muscle under the cold exposure conditions used).z 1998 Federation of European Biochemical Societies.

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Section: Discussionsupporting

confidence: 93%

Thermoregulatory uncoupling in heart muscle mitochondria: involvement of the ATP/ADP antiporter and uncoupling protein

Simonyan

Skulachev

1998

FEBS Letters

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“…Hyperthyroidy was responsible for a decrease in the ⌬⌿ mito as assessed in intact cells, which is in favor of a primary increase in slippage responsible for a decreased membrane potential. Several reports in the literature have investigated the relationship between mitochondrial membrane potential and hyperthyroidy, and the results are conflicting, probably depending on the experimental tool used for assessing membrane potential in intact cells (5,8,(51)(52)(53)(54). This could also explain the decrease in the overall coupling in oxidative phosphorylation (ATP/O ratio) when oxidative phosphorylation flux increases (Figs.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Respiratory Chain Adjustment to Cellular Energy Demand

Nogueira

Rigoulet

Piquet

et al. 2001

Journal of Biological Chemistry

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Because adaptation to physiological changes in cellular energy demand is a crucial imperative for life, mitochondrial oxidative phosphorylation is tightly controlled by ATP consumption. Nevertheless, the mechanisms permitting such large variations in ATP synthesis capacity, as well as the consequence on the overall efficiency of oxidative phosphorylation, are not known. By investigating several physiological models in vivo in rats (hyper-and hypothyroidism, polyunsaturated fatty acid deficiency, and chronic ethanol intoxication) we found that the increase in hepatocyte respiration (from 9.8 to 22.7 nmol of O 2 /min/mg dry cells) was tightly correlated with total mitochondrial cytochrome content, expressed both per mg dry cells or per mg mitochondrial protein. Moreover, this increase in total cytochrome content was accompanied by an increase in the respective proportion of cytochrome oxidase; while total cytochrome content increased 2-fold (from 0.341 ؎ 0.021 to 0.821 ؎ 0.024 nmol/mg protein), cytochrome oxidase increased 10-fold (from 0.020 ؎ 0.002 to 0.224 ؎ 0.006 nmol/mg protein). This modification was associated with a decrease in the overall efficiency of the respiratory chain. Since cytochrome oxidase is well recognized for slippage between redox reactions and proton pumping, we suggest that this dramatic increase in cytochrome oxidase is responsible for the decrease in the overall efficiency of respiratory chain and, in turn, of ATP synthesis yield, linked to the adaptive increase in oxidative phosphorylation capacity.In aerobic living systems, oxidative phosphorylation activity can vary widely to adequately match ATP synthesis to energy demand according to physiological or pathological conditions. In contrast to short-term adaptation, which relies only on a flux modulation through every functional unit of mitochondrial oxidative phosphorylation, chronic adaptation to various rates of ATP utilization can also be achieved by modifying the number of these functional units (mitogenesis). Indeed, in the light of the large physiological variations in ATP turnover observed in living systems, it is highly probable that the amount of enzymes involved in the oxidative phosphorylation pathway plays a significant role. Recently the trade-off between rate and yield of ATP synthesis in heterotrophic organisms has been highlighted as a possible major mechanism of cooperation and competition involved in the evolutionary aspects of energy metabolism (1).By investigating the effect on the yield of ATP synthesis (ATP/O) 1 after acute modulations of the flux through the oxidative phosphorylation pathway in yeast mitochondria, it has been shown that the decrease in flux was accompanied by an increase in efficiency when the flux was limited by substrate supply (2-4). Conversely, no change in ATP/O was observed when the oxidative phosphorylation flux was modulated by the inhibition of ATP synthesis (oligomycin) (2-4). Hence, depending on the mechanism permitting to modulate the flux through the respiratory chain, different cons...

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“…In hepatocytes of thyrotoxic rats, approximately 50% of the increase in cellular oxygen consumption was accounted for by an increased rate of mitochondrial H + leakage [69]. Experiments using JC-1, a mitochondrial membrane potential (DYm) probe, revealed that hepatocytes from rats with different thyroid status present a decrease in the membrane potential and an increase in respiration [70]. In thyrotoxic human skeletal muscle, there is an~70% increase in the Krebs cycle flux and no increase in ATP synthesis [71].…”

Section: Thyroid Hormone-dependent Thermogenic Mechanisms In Skeletalmentioning

confidence: 99%

Adaptive Activation of Thyroid Hormone and Energy Expenditure

et al. 2005

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The mechanisms by which thyroid hormone accelerates energy expenditure are poorly understood. In the brown adipose tissue (BAT), activation of thyroid hormone by type 2 iodothyronine deiodinase (D2) has been known to play a role in adaptive energy expenditure during cold exposure in human newborns and other small mammals. Although BAT is not present in significant amounts in normal adult humans, recent studies have found substantial amounts of D2 in skeletal muscle, a metabolically relevant tissue in humans. This article reviews current biological knowledge about D2 and adaptive T3 production and their roles in energy expenditure.

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Decrease in mitochondrial energy coupling by thyroid hormones: a physiological effect rather than a pathological hyperthyroidism consequence

Cited by 41 publications

References 47 publications

Thermoregulatory uncoupling in heart muscle mitochondria: involvement of the ATP/ADP antiporter and uncoupling protein

Thermoregulatory uncoupling in heart muscle mitochondria: involvement of the ATP/ADP antiporter and uncoupling protein

Mitochondrial Respiratory Chain Adjustment to Cellular Energy Demand

Adaptive Activation of Thyroid Hormone and Energy Expenditure

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