Physiological Importance of the T3 Mitochondrial Pathway

Wrutniak, Chantal; Rochard, Pierrick; Casas, François; Fraysse, Å. Staffan; Charrier, J.; Cabello, Gérard

doi:10.1111/j.1749-6632.1998.tb10738.x

Cited by 41 publications

(19 citation statements)

References 32 publications

(49 reference statements)

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“…Moreover, in contrast to p28, this protein harbours the DNA-binding domain of the T3 nuclear receptor. Interestingly, gel shift experiments established that p43 efficiently bound to four sequences of the mitochondrial genome previously identified (Wrutniak et al 1998, Casas et al 1999, sharing strong homologies with T3 REs described on nuclear genes. Last, in organello transcription experiments demonstrated that p43 strongly increases mitochondrial genome transcription, and, as a consequence, mitochondrial protein synthesis (Casas et al 1999).…”

Section: Thyroid Hormone Influence On Mitochondrial Genome Expressionmentioning

confidence: 98%

Thyroid hormone action in mitochondria

Wrutniak‐Cabello¹,

Casas²,

Cabello³

2001

Journal of Molecular Endocrinology

275

175

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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: Thyroid Hormone Influence On Mitochondrial Genome Expressionmentioning

confidence: 98%

Thyroid hormone action in mitochondria

Wrutniak‐Cabello¹,

Casas²,

Cabello³

2001

Journal of Molecular Endocrinology

275

175

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“…A new transcription factor, MTERF3, acting as a negative regulator of mitochondrial transcription, has been added to the list of mitochondrial transcription factors. The sites on the genome of the predicted (12, 13, 88) and experimentally verified (14,16,18,(89)(90)(91) binding sites for steroid and thyroid hormone receptors are depicted: red triangles, HREs for class I receptors (consensus sequence, AGAACAxxxTGTTCT), black triangles, HREs for class II receptors (consensus sequence AGGTCAxxxTGACCT). Mutations not only of the structural genes but also of regulatory sites of the genome (D-loop), can be linked to disease states.…”

Section: Role Of Mitochondrial Steroid Hormone Receptors In Apoptosismentioning

confidence: 99%

“…The steroid and thyroid hormones also exert rapid effects by way of membrane bound receptors-classical, G-protein associated, or still unidentified molecules (7)(8)(9)(10) resulting in modulation of membrane, cytoplasmic, and/or nuclear associated processes (11). The detection of steroid and TRs in mitochondria of a variety of cells raised the question as to the role of these agents in mitochondrial physiology and in the coordination of processes necessitating the involvement of both nuclear and mitochondrial actions (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

Steroid and thyroid hormone receptors in mitochondria

2008

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SummaryReceptors for glucocorticoids, estrogens, androgens, and thyroid hormones have been detected in mitochondria of various cell types by Western blotting, immunofluorescence labeling, confocal microscopy, and immunogold electron microscopy. A role of these receptors in mitochondrial transcription, OXPHOS biosynthesis, and apoptosis is now being revealed. Steroid and thyroid hormones regulate energy production, inducing nuclear and mitochondrial OXPHOS genes by way of cognate receptors. In addition to the action of the nuclearly localized receptors on nuclear OXPHOS gene transcription, a parallel direct action of the mitochondrially localized receptors on mitochondrial transcription has been demonstrated. The coordination of transcription activation in nuclei and mitochondria by the respective receptors is in part realized by their binding to common trans acting elements in the two genomes. Recent evidence points to a role of the mitochondrial receptors in cell survival and apoptosis, exerted by genomic and nongenomic mechanisms. The identification of additional receptors of the superfamily of nuclear receptors and of other nuclear transcription factors in mitochondria increases their arsenal of regulatory molecules and further underlines the central role of these organelles in the integration of growth, metabolic, and cell survival signals.2008 IUBMB IUBMB Life, 60(4): [210][211][212][213][214][215][216][217][218][219][220][221][222][223] 2008

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“…Certainly, in fetal sheep, there is an increase in the proportion of the anaerobic type II muscle fibers in several muscles after fetal thyroidectomy consistent with the more limited oxidative capacity observed in these circumstances (Finkelstein et al 1991, Fowden & Silver 1995. At the cellular level, thyroid hormones can influence oxidative metabolism either by changing expression and activity of the electrogenic Na C -K C ATPase pump or by acting on the mitochondrial electron transport chain (ETC) and oxidative phosphorylation per se (Wrutniak et al 1998, Ramminger et al 2002, Patel et al 2011. In vitro studies have shown that T 4 and T 3 increase the amount and activity of Na C -K C ATPase pumps in cultured skeletal myotubes and pulmonary epithelial cells from fetal rats close to term (Brodie & Sampson 1988, Ramminger et al 2002.…”

Section: Metabolic Effects Of the Thyroid Hormonesmentioning

confidence: 99%

Thyroid hormones in fetal growth and prepartum maturation

Forhead

Fowden

2014

Journal of Endocrinology

342

270

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The thyroid hormones, thyroxine (T 4 ) and triiodothyronine (T 3 ), are essential for normal growth and development of the fetus. Their bioavailability in utero depends on development of the fetal hypothalamic-pituitary-thyroid gland axis and the abundance of thyroid hormone transporters and deiodinases that influence tissue levels of bioactive hormone. Fetal T 4 and T 3 concentrations are also affected by gestational age, nutritional and endocrine conditions in utero, and placental permeability to maternal thyroid hormones, which varies among species with placental morphology. Thyroid hormones are required for the general accretion of fetal mass and to trigger discrete developmental events in the fetal brain and somatic tissues from early in gestation. They also promote terminal differentiation of fetal tissues closer to term and are important in mediating the prepartum maturational effects of the glucocorticoids that ensure neonatal viability. Thyroid hormones act directly through anabolic effects on fetal metabolism and the stimulation of fetal oxygen consumption. They also act indirectly by controlling the bioavailability and effectiveness of other hormones and growth factors that influence fetal development such as the catecholamines and insulin-like growth factors (IGFs). By regulating tissue accretion and differentiation near term, fetal thyroid hormones ensure activation of physiological processes essential for survival at birth such as pulmonary gas exchange, thermogenesis, hepatic glucogenesis, and cardiac adaptations. This review examines the developmental control of fetal T 4 and T 3 bioavailability and discusses the role of these hormones in fetal growth and development with particular emphasis on maturation of somatic tissues critical for survival immediately at birth.

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Physiological Importance of the T3 Mitochondrial Pathway

Cited by 41 publications

References 32 publications

Thyroid hormone action in mitochondria

Thyroid hormone action in mitochondria

Steroid and thyroid hormone receptors in mitochondria

Thyroid hormones in fetal growth and prepartum maturation

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