Evidence for the rapid direct control both <i>in vivo</i> and <i>in vitro</i> of the efficiency of oxidative phosphorylation by 3,5,3′-tri-iodo-<scp>l</scp>-thyronine in rats

Palacios-Romero, R; Mowbray, John

doi:10.1042/bj1840527

Cited by 57 publications

(46 citation statements)

References 61 publications

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“…Rapidity, refractoriness to inhibitors of protein synthesis, and occurrence in the absence of nuclei ruled out the involvement of the T3 genomic pathway. Parallel to this, several studies have demonstrated that the mitochondrion is a major compartment of T3 accumulation in the cell (Palacios-Romero & Mowbray 1979, Sterling et al 1984b, Hashizume et al 1986, Morel et al 1996. These data led to the proposition that ANT was a major T3 target involved in the short-term influence of the hormone on the organelle.…”

Section: Short-term Influencementioning

confidence: 93%

Thyroid hormone action in mitochondria

Wrutniak‐Cabello¹,

Casas²,

Cabello³

2001

Journal of Molecular Endocrinology

268

169

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Triiodothyronine (T3) is considered a major regulator of mitochondrial activity. In this review, we show evidence of the existence of a direct T3 mitochondrial pathway, and try to clarify the respective importance of the nuclear and mitochondrial pathways for organelle activity. Numerous studies have reported short-term and delayed T3 stimulation of mitochondrial oxygen consumption. Convincing data indicate that an early influence occurs through an extra-nuclear mechanism insensitive to inhibitors of protein synthesis. Although it has been shown that diiodothyronines could actually be T3 mediators of this short-term influence, the detection of specific T3-binding sites, probably corresponding to a 28 kDa c-Erb A 1 protein of the inner membrane, also supports a direct T3 influence. The more delayed influence of thyroid hormone upon mitochondrial respiration probably results from mechanisms elicited at the nuclear level, including changes in phospholipid turnover and stimulation of uncoupling protein expression, leading to an increased inner membrane proton leak. However, the involvement of a direct mitochondrial T3 pathway leading to a rapid stimulation of mitochondrial protein synthesis has to be considered.Both pathways are obviously involved in the T3 stimulation of mitochondrial genome transcription. First, a 43 kDa c-Erb A 1 protein located in the mitochondrial matrix (p43), acting as a potent T3-dependent transcription factor of the mitochondrial genome, induces early stimulation of organelle transcription. In addition, T3 increases mitochondrial TFA expression, a mitochondrial transcription factor encoded by a nuclear gene. Similarly, the stimulation of mitochondriogenesis by thyroid hormone probably involves both pathways. In particular, the c-erb A gene simultaneously encodes a nuclear and a mitochondrial T3 receptor (p43), thus ensuring coordination of the expression of the mitochondrial genome and of nuclear genes encoding mitochondrial proteins.Recent studies concerning the physiological importance of the direct mitochondrial T3 pathway involving p43 led to the conclusion that it is not only involved in the regulation of fuel metabolism, but also in the regulation of cell differentiation. As the processes leading to or resulting from differentiation are energy-consuming, p43 coordination of metabolism and differentiation could be of significant importance in the regulation of development.

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Section: Short-term Influencementioning

confidence: 93%

Thyroid hormone action in mitochondria

Wrutniak‐Cabello¹,

Casas²,

Cabello³

2001

Journal of Molecular Endocrinology

268

169

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“…They were fasted overnight and, where appropriate, given 1 nmolj100 g body weight of triiodo-L-thyronine prior to sacrifice [3].…”

Section: Animalsmentioning

confidence: 99%

“…Mitochondria have been shown to acquire iodine [2] and triiodothyronine [3] at very short times after radiohormone administration to hypothyroid animals and a proteolipid fraction with specific tight binding sites for the hormone has been isolated from rat liver mitochondrial inner membrane [4].…”

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confidence: 99%

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

Mowbray¹,

Corrigall²

1984

European Journal of Biochemistry

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1. An improved simple technique for measuring adenine nucleotide translocator activity at low medium substrate concentrations is described.2. Confirming previous reports, thyroidectomy was shown to lead to lowered translocator activity in rat liver mitochondria. The rapidly exchangeable portion of the matrix nucleotide also decreased in hypothyroid preparations even though the total nucleotides increased substantially.3. The apparent K,,, of translocator for ADP increased from 2.8 to 6.2pM in hypothyroid preparations: Mg2+ ions raised this to about 20 pM.4. All of these changes in adenine nucleotide translocation were entirely reversed by 15min after a single intravenous near-physiological dose of triiodothyronine.The mitochondrion has long been considered a likely subcellular target of thyroid hormone action (review [I]). Mitochondria have been shown to acquire iodine [2] and triiodothyronine [3] at very short times after radiohormone administration to hypothyroid animals and a proteolipid fraction with specific tight binding sites for the hormone has been isolated from rat liver mitochondrial inner membrane [4].Rapid effects of hormone on oxidative phosphorylation have also been observed. Hoch [2] found changes in respiratory control and uncoupler sensitivity 2 min after thyroxine injection to hypothyroid rats; Sterling and his co-workers have reported increased phosphorylation in sub-mitochondrial vesicles both using direct addition of nanomolar hormone concentrations [5] and with vesicles prepared 30 rnin after injection of a near-physiological dose of triiodothyronine [I]. 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. 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). mals: in experiments with normal animals, the same group [12] had shown that a single large dose of triiodothyronine increased translocator activi...

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“…Short-term effects of thyroid hormones include, among others: (1) an increase of oligomycin-sensitive oxygen consumption after addition of T 3 to the perfusion medium of liver from hypothyroid rats [4]; (2) a fall in the mitochondrial ATP/ADP ratio under the conditions of 1) [5] (3) a rapid stimulation of hepatocyte oxygen consumption in the presence of cycloheximide [6]; (4) a rapid increase of ATP synthesis within minutes [7]; and (5) an increase in the P/O ratio of liver mitochondria isolated 15 min after injection of T 3 into thyroidectomized rats [8].…”

Section: Introductionmentioning

confidence: 99%

Interaction of diiodothyronines with isolated cytochromec oxidase

et al. 1994

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Diiodothyronines (3,3'-T2 and 3,5-T2) stimulate the activity of isolated cytochrome c oxidase (COX) from bovine heart mitochondria. Maximal stimulation of activity (about 50%) is obtained with 3,3'-T2 at pH 6.4 and with 3,5-T2 at pH 7.4. In contrast, 3,5,3'-triiodothyronine (TO exhibited no or little stimulation of COX activity. Binding of the hormones to COX leads to conformational changes as shown by modified visible spectra of the oxidized enzyme. It is suggested that 'short-term' effects of thyroid hormones on mitochondrial respiration are at least partly due to the allosteric interaction of diiodothyronines with the COX complex.

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Evidence for the rapid direct control both in vivo and in vitro of the efficiency of oxidative phosphorylation by 3,5,3′-tri-iodo-l-thyronine in rats

Cited by 57 publications

References 61 publications

Thyroid hormone action in mitochondria

Thyroid hormone action in mitochondria

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

Interaction of diiodothyronines with isolated cytochromec oxidase

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