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Endocrinology Vol. 138, No. 2 764-770
Copyright © 1997 by The Endocrine Society

Articles

Thyroid Hormones Regulate the Onset of Osmotic Activity of Rat Liver Mitochondria after Birth1

A. Almeida2, C. Lopez-Mediavilla and J. M. Medina

Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain

Address all correspondence and requests for reprints to: J. M. Medina, Departamento de Bioquímica y Biología Molecular, Edificio Departamental, Universidad de Salamanca, Avda Campo Charro s/n, 37007 Salamanca, Spain.


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
The effect of thyroid hormone deprivation on the osmotic activity of liver mitochondria from early newborn rats was studied. Experimentally induced hypothyroidism prevented the increase in the osmotic activity of mitochondria observed immediately after birth. Osmotic activity was restored by T4 and T3 treatment to hypothyroid newborns but not when this treatment was supplemented with cycloheximide. Under the same circumstances, streptomycin had no effect. Hypothyroidism abolished the change in the slope of the osmotic curve (plot of inverse absorbance of mitochondrial suspensions incubated in sucrose solutions vs. inverse sucrose concentration) observed in mitochondria from euthyroid newborns at 110–120 mOsm sucrose, suggesting that hypothyroidism prevents the formation of tight physical connections between mitochondrial outer and inner membranes. Thyroid hormone deprivation increased the passive permeability of the mitochondrial inner membrane to protons, resulting in a decreased respiratory control ratio. Hypothyroidism prevented the sharp decrease in the affinity of mitochondria for ATP observed in euthyroid newborns immediately after birth. These results corroborate our previous suggestion that, during the early neonatal period, thyroid hormones control the synthesis of some nucleus-coded protein(s) involved in the assembly of F0,F1-ATPase.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
FETAL RAT liver mitochondria have a relatively permeable inner membrane, which correlates with a low respiratory control ratio (RCR) (1). Immediately after birth, however, rat liver mitochondria undergo many significant changes in structure and function. Thus, the inner mitochondrial membrane undergoes a maturation process through which it changes from the relatively permeable membrane observed in the fetus to the fully osmotically active membrane found in the early newborn (1, 2, 3). This process correlates with postnatal acquisition of an efficient energy-transducing machinery within the first hour after birth, as shown by the sharp increase in the RCR (1, 4, 5) and in the activities of mitochondrial respiratory complexes (4). Postnatal mitochondrial enrichment in adenine nucleotides (4) has been reported to promote ultrastructural changes that result in a rapid increase in their osmotic activity (1, 6). The effect of adenine nucleotides may be caused by an interaction between ATP and some specific protein of the mitochondrial inner membrane (1, 2, 3, 5, 6)

Thyroid hormones are known to play an important role in the regulation of the differentiation, development, and growth of most mammalian tissues (7). Mitochondria are considered to be subcellular targets of thyroid hormone action because they affect mitochondrial numbers, morphology (8, 9), molecular structure (10, 11), and function (12). In addition, T4 and T3, also play an important role in the postnatal differentiation and proliferation of liver mitochondria (13). Thus, thyroid hormones regulate the gene expression of the ß-catalytic subunit of the mitochondrial F0,F1-ATPase complex (14, 15), considered to be a marker protein of mitochondrial biogenesis during development (4). Along the same line, we recently have shown that thyroid hormones play an important role in postnatal mitochondrial differentiation, as shown by the low RCR and the low activity of the F0,F1-ATPase found in liver mitochondria from hypothyroid newborns (16).

Since Tedeschi and Harris (17) first established a quantitative relationship between absorbance and matrix volume, several authors (18, 19, 20) have developed the use of the absorbance of mitochondrial suspensions as a quantitative method for measuring changes in mitochondrial structure. Thus, mitochondria expand in hyposmotic medium, and this is accompanied by a decrease in the absorbance of the mitochondrial suspension (1, 18, 20). Nonlinearities on the absorbance osmotic curve depend specifically on mitochondrial structure (17, 18, 20). The changes observed in the osmotic curve of mitochondria from hypothyroid newborns may be explained in terms of structural alterations caused by hypothyroidism on the organelle. The aim of the present work was to study the effect of experimental hypothyroidism on the osmotic properties of liver mitochondria during the first hour of extrauterine life. In addition, the effect of hypothyroidism on the passive permeability of the mitochondrial inner membrane to protons was studied.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Chemicals
Methimazole (MMI), propylthiouracil (PTU), T4, T3, cycloheximide, streptomycin, and oligomycin were purchased from Sigma Chemical Co. (St Louis, MO). Percoll was obtained from Pharmacia (Uppsala, Sweden). Standard analytical grade laboratory reagents were from Merck (Darmstad, Germany) or Sigma.

Animals
Pregnant albino Wistar rats were fed ad libitum on a stock laboratory diet (carbohydrates 49.8%, protein 23.5%, fat 3.7%, minerals 5.5%, and added vitamins and amino acids). Maternal and fetal hypothyroidism was induced by the administration of 0.02% MMI or 0.05% PTU in the drinking water of pregnant rats from day 14 of gestation (16). Fetuses were delivered on 21.5 days of gestation (21.7 days for full gestation) by rapid hysterectomy after cervical dislocation of the mother. In experiments in which the effect of thyroid hormone supplement was investigated, hypothyroid newborns were injected ip at birth with a solution of 0.9% NaCl containing 3.6 and 14.4 µg/100 g BW of T3 and T4, respectively (14, 15, 16). To inhibit cytosolic or mitochondrial protein synthesis, newborns were injected at birth with T4 and T3 solution supplemented with 1 mg/100 g BW of cycloheximide or 10 mg/100 g BW of streptomycin, respectively (16). Littermates were injected with the same vol (50 µl) of vehicle. After treatments, newborns were kept in an incubator at 37 C for 1 h with a continuous stream of water-saturated air.

Isolation of liver mitochondria
Newborns were killed by decapitation at the times indicated in the figure legends (0 h or 1 h after birth), and their livers were homogenized in an isolation medium containing 250 mM sucrose, 1 mM EDTA, and 10 mM HEPES, pH 7.4 (1/4, wt/vol). The whole mitochondrial fraction was isolated from liver homogenates by a discontinuous Percoll gradient technique (21, 22). Mitochondrial protein was determined by the method of Lowry et al. (23).

Measurement of mitochondrial swelling
Osmotically induced swelling was studied at 30 C in suspensions containing 0.1 mg mitochondrial protein and varying concentrations of sucrose. Mitochondria were incubated with gentle stirring for 5 min at 30 C in 250 µl sucrose solutions at a final osmolality ranging between 40 and 250 mOsm. The absorbance of mitochondrial suspensions was measured with a Reader 340 ATTC enzyme-linked immunosorbent assay (SLT Labinstruments, Salzburg, Austria) fitted with a 540-nm filter. Changes in A at 540 nm were taken as an indication of changes in mitochondrial diameter (1, 18, 20). When the effect of ATP on mitochondrial swelling was studied, ATP was added to mitochondrial suspensions at a final concentration ranging between 0.05 and 0.4 mM, and mitochondrial incubation was carried out as described above.

If it is assumed that ATP induces mitochondrial contraction by binding to some specific site of the mitochondrial inner membrane (1, 2, 3, 6, 19), the apparent dissociation constant (Ks). of ATP can be defined as the effectiveness of ATP to produce changes in mitochondrial diameter. Ks was determined as described by Stoner and Sirak (19); mitochondria (0.1 mg mitochondrial protein) were incubated for 5 min in 250 µl of 250 mOsm sucrose solution containing 0.05, 0.1, 0.2, 0.3, or 0.4 mM ATP. The A of mitochondrial suspensions was measured at 540 nm and the contraction of mitochondria was calculated from the percent increase in the absorbance of mitochondrial suspensions for each concentration of ATP. The Ks was determined by plotting 1/[ATP] vs. 1/mitochondrial contraction (19), yielding a straight line which crosses the x axis at Ks.

Measurement of mitochondrial respiratory parameters
The rate of oxygen consumption was measured using a Clark-type electrode (Gilson, Medical Electronic, France) in a thermostatically controlled (30 C) and magnetically stirred incubation chamber of 1.8 ml capacity. Respiratory measurements were carried out in respiration medium containing 225 mM sucrose, 10 mM succinate, 10 mM KCl, 5 mM MgCl2, 10 mM KH2PO4, 1 mM EDTA, and 10 mM Tris, pH 7.4. Respiration in state 4 in the presence of oligomycin (state 4oi) was initiated by adding 5 µl oligomycin (2 mg/ml). State 3 respiration was initiated by adding 200 nmol of ADP. Respiratory parameters were expressed as nanoatoms of oxygen consumed/minute per milligram of mitochondrial protein. The RCR is the ratio between oxygen consumption in state 3 and state 4.

Statistical analyses
Statistical analyses of the results were performed by one-way ANOVA, followed by a least-significant difference multiple-range test.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Effect of experimental hypothyroidism on the osmotic activity of liver mitochondria during early development
Figure 1Go shows the changes in mitochondrial absorbance associated with osmotically induced swelling of liver mitochondria from euthyroid (EU) or hypothyroid (MMI or PTU) newborns. In agreement with previous work (1, 6), there was a definite correlation between the osmotic activity of the mitochondrial inner membrane and increasing developmental age in EU newborns. Thus, mitochondria from EU fetuses (0 h postpartum) showed an osmotically inactive inner membrane, which became active within the first hour after birth (Fig. 1Go). However, hypothyroidism caused by MMI or PTU treatment blocked postnatal increase in mitochondrial osmotic activity, the osmotic activity of mitochondria in hypothyroid fetuses being very similar to that observed in hypothyroid newborns (Fig. 1Go). To determine whether these findings were caused by the experimentally induced hypothyroidism, thyroid hormones were administered to hypothyroid newborns at birth and mitochondrial osmotic activity was determined 1 h later (see Materials and Methods). Under these circumstances, thyroid hormones promoted a postnatal increase in the osmotic activity of the mitochondrial inner membrane, a pattern very similar to that found in age-matched EU newborns being observed (Fig. 1Go).



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  		Figure 1. Effect of hypothyroidism on the osmotic activity of liver mitochondria from newborn rats. Liver mitochondria were isolated from EU or hypothyroid (MMI and PTU) festuses (0 h) and from EU, hypothyroid or T4- and T3-treated hypothyroid newborns (1 h) and were incubated at a concentration of 0.1 mg of protein in 250 µl of sucrose solution at 30 C for 5 min. Changes in absorbance (A) of mitochondrial suspensions were recorded at 540 nm. Values are means ± SEM of four different mitochondrial preparations for each experimental condition. The slope of the first part of the curve from hypothyroid newborns was statistically different (P < 0.001) from those from EU and T4+T3-treated hypothyroid newborns.

 
Figure 2Go shows the osmotic equilibrium curves resulting from plotting inverse absorbance vs. inverse osmolality. The osmotic curve observed in mitochondria from 1-h-old EU newborns can be divided into three linear regions separated by well-defined breaks at 110–120 and 60–70 mOsm, as described previously for adult rat liver mitochondria (18, 20). However, the osmotic curve of mitochondria from EU fetuses was divided only into two different linear regions separated by a break at 60–70 mOsm, the break at 110–120 mOsm not being apparent (Fig. 2Go). The osmotic curves of mitochondria from both hypothyroid fetuses and newborns were very similar to those observed for EU fetuses, in which only one break (60–70 mOsm) was apparent. It should be noted that thyroid hormone administration to hypothyroid newborns at birth restored the first break in the osmotic curve (110–120 mOsm), a pattern very similar to that of EU newborns (Fig. 2Go).



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  		Figure 2. Effect of hypothyroidism on the osmotic curve of liver mitochondria from newborn rats. Values of inverse absorbance (A-1) are plotted vs. inverse osmolality of the suspending medium. EU newborns, upper panel; MMI-treated newborns, lower panel. Results obtained with PTU-treated newborns were not different from those of MMI-treated newborns and are not shown. Arrows indicate transition points of the osmotic curves at which the slope changes (P < 0.01).

 
To determine whether the effect of thyroid hormones on the postnatal changes in the osmotic activity of the mitochondrial inner membrane might be mediated by protein synthesis, cycloheximide or streptomycin (which are inhibitors of cytoplasmatic or mitochondrial-encoded protein synthesis, respectively) were administered together with T4 and T3 to hypothyroid newborns at birth (see Materials and Methods). Treatment with cycloheximide, but not with streptomycin, prevented the effect of thyroid hormones on the osmotic activity of the mitochondrial inner membrane (Fig. 3Go). Thus, the osmotic curve of mitochondria from hypothyroid newborns treated with cycloheximide together with T4 and T3 (Fig. 3Go) was very similar to that observed for untreated hypothyroid newborns (Fig. 2Go).



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  		Figure 3. Effect of protein synthesis inhibitors on the osmotic activity of liver mitochondria from T4- and T3-treated hypothyroid newborn rats. Liver mitochondria were isolated from 1-h-old hypothyroid (MMI) newborns treated at birth with T4 and T3 (T4+T3), T4 and T3 plus streptomycin (T4+T3+St) or T4 and T3 plus cycloheximide (T4+T3+Cy). Mitochondria were incubated at a concentration of 0.1 mg protein in 250 µl sucrose solution at 30 C for 5 min. Changes in absorbance (A) of mitochondrial suspensions were recorded at 540 nm. Values are means ± SEM of three different mitochondrial preparations for each experimental condition. Arrows indicate transition points of the osmotic curves at which the slope changes (P < 0.01). The slope of the first part of the curve from T4+T3+Cy-treated hypothyroid newborns was statistically different (P < 0.001) from those from T4+T3-and T4+T3+St-treated hypothyroid newborns. Results obtained with PTU-treated newborns were not different from those of MMI-treated newborns and are not shown.

 
Effect of experimental hypothyroidism on the passive permeability of the mitochondrial inner membrane to protons during early development
To relate the findings on osmotic activity with possible changes in the passive permeability of the mitochondrial inner membrane to protons, we investigated the effect of experimental hypothyroidism on oxygen consumption in state 4 in the presence of oligomycin, a potent inhibitor of mitochondrial F0,F1-ATPase, (state 4oi). Under these circumstances, the passive permeability to protons of the mitochondrial inner membrane is measured (16). In agreement with our previous work (16), liver mitochondria from hypothyroid newborns were found to show a significant decrease in the RCR, with respect to the values found in liver mitochondria from EU newborns (Fig. 4Go). The administration of thyroid hormones to hypothyroid newborns at birth increased the RCR to values similar to those found in mitochondria from EU newborns. The effect of T4 and T3 on RCR was blocked by cycloheximide supplement but not by streptomycin, (Fig. 4Go). In addition, the decrease in the RCR caused by hypothyroidism (Fig. 4Go) was mainly because of an increase in the rate of oxygen consumption in state 4 of respiration. Moreover, a significant increase in the passive permeability of the mitochondrial inner membrane to protons, i.e. the rate of oxygen consumption in state 4oi, was observed in hypothyroid newborns. T4 and T3 administration to hypothyroid newborns at birth reversed the effects of hypothyroidism on respiratory parameters; these effects of thyroid hormone administration to hypothyroid newborns were blocked by cycloheximide but not by streptomycin (Fig. 4Go).



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  		Figure 4. Effect of hypothyroidism on the RCR and on the rate of respiration in state 4 of liver mitochondria from newborn rats. Liver mitochondria were isolated from EU, hypothyroid (MMI), T4-, and T3-treated hypothyroid (MMI+T), T4 and T3 plus streptomycin-treated hypothyroid (MMI+T+St) or T4 and T3 plus cycloheximide-treated hypothyroid (MMI+T+Cy) newborns (1 h). The rates of respiration in state 4 and in state 4oi (in the presence of 5 µg/ml oligomycin) are expressed as nanoatoms of oxygen/min per mg of mitochondrial protein. Values are means ± SEM of four mitochondrial preparations for each experimental condition. *, P < 0.05; **, P < 0.01;***, P < 0.001, when compared with EU values. #, P < 0.05; ##, P < 0.01; ###, P < 0.001, when compared with MMI+T values. Results obtained with PTU-treated newborns were not different from those of MMI-treated newborns and are not shown.

 
Effect of ATP on the osmotic activity of liver mitochondria from hypothyroid newborns
Adenine nucleotides induce contraction of the mitochondrial inner membrane, inhibiting the osmotically induced swelling in liver mitochondria from both newborn (1) and adult rats (19). This prompted us to investigate the effect of ATP on the osmotic activity of liver mitochondria from hypothyroid newborns. Preincubation of liver mitochondria with increasing concentrations of ATP inhibited osmotically induced mitochondrial swelling (Fig. 5Go).



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  		Figure 5. Effect of ATP on osmotically induced swelling of liver mitochondria from hypothyroid newborn rats. Liver mitochondria were isolated from EU, hypothyroid (MMI), or T4- and T3-treated hypothyroid newborns (1 h) and were incubated at a concentration of 0.1 mg protein in 250 µl sucrose solution containing increasing concentrations of ATP at 30 C for 5 min. Changes in absorbance (A) of mitochondrial suspension were recorded at 540 nm. Data are from a representative experiment. Results obtained with PTU-treated newborns were not different from those of MMI-treated newborns and are not shown.

 
To quantify the effectiveness of ATP in inhibiting mitochondrial swelling, the apparent Ks was determined as described by Stoner and Sirak (19) (see Materials and Methods). The value of Ks increased sharply during the first hour of extrauterine life (P < 0.001) in liver mitochondria from EU newborns (Fig. 6Go). However, hypothyroidism caused by MMI or PTU treatment blocked the postnatal increase in the Ks, although thyroid hormone administration to hypothyroid newborns reversed the effects caused by hypothyroidism. In addition, the effects of thyroid hormone treatment to hypothyroid newborns was prevented by cycloheximide but not by streptomycin supplementation (Fig. 6Go).



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  		Figure 6. Effect of hypothyroidism on the Ks of liver mitochondria for ATP during early development. Liver mitochondria were isolated from EU or hypothyroid (MMI and PTU) festuses (0 h) and from EU, hypothyroid, T4-, and T3-treated hypothyroid (T4+T3), T4, and T3 plus streptomycin-treated hypothyroid (T4+T3+St) or T4 and T3 plus cycloheximide-treated hypothyroid (T4+T3+Cy) newborns (1 h) and were incubated at a concentration of 0.1 mg protein in 250 µl 250 mOsm sucrose solution containing 0.05–0.4 mM ATP at 30 C for 5 min. Absorbance of mitochondrial suspensions was measured at 540 nm. Mitochondrial contraction was calculated from the percent increase in the absorbance for each concentration of ATP. The Ks was determined by plotting 1/[ATP] vs. 1/mitochondrial contraction, yielding a straight line that crosses the x axis at the Ks value. Values are means ± SEM of three different mitochondrial preparations for each experimental condition. ***, P < 0.001, when compared with EU values. ###, P < 0.001, when compared with T4+T3 values.

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
We have recently reported that hypothyroidism inhibits the postnatal changes in rhodamine-123-stained mitochondrial populations occurring immediately after birth. This results in a decrease in the proportion of the mature form of mitochondria, together with an impairment of mitochondrial respiratory function. These effects probably can be accounted for by the inhibition of the synthesis of some nucleus-coded protein(s) involved in F0,F1-ATPase assembly (16). In the present work, we studied whether these changes were correlated to modifications in mitochondrial structure affecting the permeability of the mitochondrial inner membrane. Indeed, our results show that hypothyroidism prevented the postnatal increase in the osmotic activity of liver mitochondria observed in EU newborns during the first hour after birth (Fig. 1Go) (1). This effect must have been caused by hypothyroidism because the administration of thyroid hormones to hypothyroid newborns at birth elicited the onset of the osmotic activity observed in EU newborns (Fig. 1Go).

When the osmotic activity of adult rat mitochondria is followed by plotting inverse absorbance vs. inverse osmolality, the osmotic curve obtained is divided into three different linear regions separated by two breaks at 110–125 and 55–70 mOsm sucrose (17, 18, 20). This osmotic behavior is attained by neonatal mitochondria within the first hour after birth (Fig. 2Go). However, the osmotic curve of mitochondria from hypothyroid newborn does not have the break at 110–120 mOsm. This effect was not observed after treatment with T4 and T3 (Fig. 2Go), suggesting that the changes in the osmotic curve of mitochondria from hypothyroid newborns were caused by thyroid hormone deficiency. Beavis and Garlid (20) have suggested that the break in the osmotic curve observed at 110–120 mOsm sucrose would be caused by the rupture of physical connections between mitochondrial outer and inner membranes. If so, our results suggest that the linkage between mitochondrial membranes, which presumably occurs within the first hour of extrauterine life, is prevented by hypothyroidism (Fig. 2Go). The recovery of osmotic activity brought about by thyroid hormone treatment was prevented by cycloheximide but not by streptomycin supplementation (Fig. 3Go). These results suggests that thyroid hormones induce physical connections between the mitochondrial outer and inner membranes through an enhancement of the synthesis of some nucleus-coded protein. It should be mentioned that the activity of creatine kinase, which is involved in physical connections between mitochondrial inner and outer membranes (24), changes with thyroid state (25).

The decrease in osmotic activity observed in mitochondria from hypothyroid newborns (Fig. 1Go) is concurrent with a decrease in the RCR (Fig. 4Go), confirming our previous results (16), to the effect that hypothyroidism prevents the development of mitochondrial respiratory function. The decrease in the RCR caused by hypothyroidism was mainly attributable to an increase in oxygen consumption in state 4oi, i.e. in the oligomycin-insensitive proton leak (Fig. 4Go), suggesting the occurrence of a high passive permeability to protons through the mitochondrial inner membrane caused by hypothyroidism (16). The effect of thyroid hormone deprivation on the RCR and the passive permeability to protons through the mitochondrial inner membrane was overcome by T4 and T3 treatment (Fig. 4Go) but was prevented when the hormones were supplemented with cycloheximide (Fig. 4Go). This is consistent with the idea that, during the postnatal period, the increase in the osmotic activity of the mitochondrial inner membrane (Fig. 1Go) would be associated with the onset of mitochondrial respiratory function. Likewise, our results suggest that both phenomena would be regulated by thyroid hormones. Our findings are insufficient, however, to decide whether T3 or its metabolite T2 (26, 27) are responsible for the effects observed in our experiments (Figs. 1Go and 4Go). Because the recovery of RCR and the osmotic activity of mitochondria from T4- and T3-treated hypothyroid newborns are sensitive to cycloheximide (Figs. 3Go and 4Go), it might be suggested that these phenomena would be regulated by T3 because the effects of T2 do not involve protein synthesis (28)

ATP inhibits the osmotically induced swelling of liver mitochondria from newborn rats (1), a phenomenon accompanied by an increase in the RCR (1, 2, 5). This effect has been interpreted in terms of an interaction of ATP with some specific protein of the mitochondrial inner membrane (1, 2, 3, 5, 6). In agreement with this, our results show that ATP inhibits mitochondrial swelling in both EU and hypothyroid newborn rats (Fig. 5Go). Nevertheless, ATP proved to be more effective in hypothyroid as compared with EU newborns, the effect being reversed by thyroid hormone treatment (Fig. 5Go). Consistent with this, the increase in the Ks of mitochondria for ATP observed during the first hour after birth in EU newborns was prevented by thyroid hormone deprivation (Fig. 6Go). This effect was reversed by thyroid hormone supplement, although the reversal was blocked by cycloheximide (Fig. 6Go). This suggests that the observed effect on Ks was achieved by some protein(s) whose synthesis is controlled by thyroid hormones. Because Ks increases as affinity decreases (19), hypothyroidism must prevent the plunge in the mitochondrial affinity for ATP occurring immediately after birth (Fig. 6Go). This suggests that, during the early neonatal period, the synthesis and assembly of a nucleus-coded protein decreases mitochondrial affinity for ATP. Because F0,F1-ATPase is the putative target of ATP under these circumstances (29, 30), such observations confirm our previous suggestion (16) that hypothyroidism would prevent the postnatal maturation of liver mitochondria through the inhibition of the synthesis of some protein presumably involved in F0,F1-ATPase assembly.

In conclusion, our results suggest that thyroid hormones regulate the postnatal acquisition of the osmotic activity of liver mitochondria through a mechanism related to the synthesis of some nucleus-coded protein(s). In addition, thyroid hormones regulate the affinity of mitochondria for ATP, suggesting that these protein(s) are involved in the assembly of the F0,F1-ATPase complex. As a consequence of the action of thyroid hormones on newborn mitochondria, the passive permeability of the mitochondrial inner membrane to protons decreases, resulting in an increase in mitochondrial respiratory function. This emphasizes the importance of thyroid hormones in controlling the postnatal maturation of liver mitochondria.


   Acknowledgments
 
The authors are grateful to J. Villoria and T. del Rey for their technical assistance.


   Footnotes
 
1 This work was supported in part by DGICYT, Spain, and the FISSS, Spain. Back

2 Recipient of an Accion de Reincorporacion from Ministerio de Educacion y Ciencia, Spain. Back

Received July 9, 1996.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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Hepatic Gene Expression Changes in Hypothyroid Juvenile Mice: Characterization of a Novel Negative Thyroid-Responsive Element
Endocrinology, August 1, 2007; 148(8): 3932 - 3940.
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 J. Nutr.Home page
T. Stites, D. Storms, K. Bauerly, J. Mah, C. Harris, A. Fascetti, Q. Rogers, E. Tchaparian, M. Satre, and R. B. Rucker
Pyrroloquinoline Quinone Modulates Mitochondrial Quantity and Function in Mice
J. Nutr., February 1, 2006; 136(2): 390 - 396.
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 Am. J. Physiol. Cell Physiol.Home page
R. Justo, J. Boada, M. Frontera, J. Oliver, J. Bermudez, and M. Gianotti
Gender dimorphism in rat liver mitochondrial oxidative metabolism and biogenesis
Am J Physiol Cell Physiol, August 1, 2005; 289(2): C372 - C378.
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