The effect of physiological doses of thyroxine on carrier-mediated ADP uptake by liver mitochondria from thyroidectomized rats

Short‐term control of mitochondrial adenine nucleotide translocator by thyroid hormone

“…Portnay et al [8] found that the lowered translocation rate was increased after 6 days of thyroxine replacement therapy to hypothyroid ani- mals: in experiments with normal animals, the same group [12] had shown that a single large dose of triiodothyronine increased translocator activity after 3 days but not significantly after 20 h. If lowered adenine nucleotide translocation can contribute, at least in some measure, to the reduced ADPjO ratio then the translocator rate ought to respond within 15 min of hormone administration just as the ratio does. This communication describes experiments which examine this possibility.…”

“…One potential component in this lowered phosphorylating ability may be the reduced rate of adenine nucleotide translocation found in hypothyroid mitochondria [8,9], since the recent elegant experiments of Tager and his co-workers [lo, 1 I] have shown that a significant measure of control of oxidative phosphorylation is exerted by the transfer. Portnay et al [8] found that the lowered translocation rate was increased after 6 days of thyroxine replacement therapy to hypothyroid ani- mals: in experiments with normal animals, the same group [12] had shown that a single large dose of triiodothyronine increased translocator activity after 3 days but not significantly after 20 h. If lowered adenine nucleotide translocation can contribute, at least in some measure, to the reduced ADPjO ratio then the translocator rate ought to respond within 15 min of hormone administration just as the ratio does.…”

“…Portnay et al [8] found that the lowered translocation rate was increased after 6 days of thyroxine replacement therapy to hypothyroid aniEnzymes. Hexokinase (EC 2.7.1.1); pyruvate kinase (EC 2.7.1.40); lactate dehydrogenase (EC 3.1.1.27); adenylate kinase (EC 2.7.4.3); glucose-6-phosphate dehydrogenase (EC 1 .I .1.49).…”

“…We have established conditions under which liver mitochondria from thyroidectomised rats show ADPjO ratios with both NAD' and FAD-linked substrates of 50-70% of those obtained using preparations from euthyroid animals with no loss of respiratory control [3,6]. Mitochondria from thyroidectomised rats isolated 15 min after intravenous injection of a physiological dose of hormone or isolated after incubation with hormone and other cell fractions showed ADPjO ratios and respiratory control ratios indistinguishable from those obtained with euthyroid preparations although the low rates of respiration per mass of protein were unchanged [3, 6, 71.One potential component in this lowered phosphorylating ability may be the reduced rate of adenine nucleotide translocation found in hypothyroid mitochondria [8,9], since the recent elegant experiments of Tager and his co-workers [lo, 1 I] have shown that a significant measure of control of oxidative phosphorylation is exerted by the transfer. Portnay et al [8] found that the lowered translocation rate was increased after 6 days of thyroxine replacement therapy to hypothyroid aniEnzymes.…”

“…One potential component in this lowered phosphorylating ability may be the reduced rate of adenine nucleotide translocation found in hypothyroid mitochondria [8,9], since the recent elegant experiments of Tager and his co-workers [lo, 1 I] have shown that a significant measure of control of oxidative phosphorylation is exerted by the transfer. Portnay et al [8] found that the lowered translocation rate was increased after 6 days of thyroxine replacement therapy to hypothyroid aniEnzymes.…”