72 research outputs found
Overexpression of the Mitochondrial T3 Receptor p43 Induces a Shift in Skeletal Muscle Fiber Types
In previous studies, we have characterized a new hormonal pathway involving a mitochondrial T3 receptor (p43) acting as a mitochondrial transcription factor and consequently stimulating mitochondrial activity and mitochondrial biogenesis. We have established the involvement of this T3 pathway in the regulation of in vitro myoblast differentiation.We have generated mice overexpressing p43 under control of the human α-skeletal actin promoter. In agreement with the previous characterization of this promoter, northern-blot and western-blot experiments confirmed that after birth p43 was specifically overexpressed in skeletal muscle. As expected from in vitro studies, in 2-month old mice, p43 overexpression increased mitochondrial genes expression and mitochondrial biogenesis as attested by the increase of mitochondrial mass and mt-DNA copy number. In addition, transgenic mice had a body temperature 0.8°C higher than control ones and displayed lower plasma triiodothyronine levels. Skeletal muscles of transgenic mice were redder than wild-type animals suggesting an increased oxidative metabolism. In line with this observation, in gastrocnemius, we recorded a strong increase in cytochrome oxidase activity and in mitochondrial respiration. Moreover, we observed that p43 drives the formation of oxidative fibers: in soleus muscle, where MyHC IIa fibers were partly replaced by type I fibers; in gastrocnemius muscle, we found an increase in MyHC IIa and IIx expression associated with a reduction in the number of glycolytic fibers type IIb. In addition, we found that PGC-1α and PPARδ, two major regulators of muscle phenotype were up regulated in p43 transgenic mice suggesting that these proteins could be downstream targets of mitochondrial activity. These data indicate that the direct mitochondrial T3 pathway is deeply involved in the acquisition of contractile and metabolic features of muscle fibers in particular by regulating PGC-1α and PPARδ
Identification of leptin receptors in human breast cancer : functional activity in the T47-D breast cancer cell line
International audienc
p28, a truncated form of TR alpha 1 regulates mitochondrial physiology
We have previously identified in mitochondria two truncated forms of the T3 nuclear receptor TR alpha 1, with molecular weights of 43kDa (p43) and 28kDa (p28) respectively located in the matrix and in the inner membrane. Previously, we have demonstrated that p43 stimulates mitochondrial transcription and protein synthesis in the presence of T3. Here we report that p28 is targeted into the organelle in a T3-dependent manner and displays an affinity for T3 higher than the nuclear receptor. We tried to generate mice overexpressing p28 using the human alpha-skeletal actin promoter, however we found an early embryonic lethality that was probably linked to a transient expression of p28 in trophoblast giant cells. This could be partly explained by the observation that overexpression of p28 in human fibroblasts induced alterations of mitochondrial physiology
Cellular localization and evolution of prolactin receptor mRNA in ovine endometrium during pregnancy
International audienc
Expression by transgenesis of a constitutively active mutant form of the prolactin receptor induces premature abnormal development of the mouse mammary gland and lactation failure
International audienc
Temperature homeostasis in mice lacking the p43 mitochondrial T3 receptor
Thyroid hormones and Thra gene play a key role in energy expenditure regulation, temperature homeostasis, and mitochondrial function. To decipher the function of the mitochondrial TRa receptor in these phenomena, we used mice lacking specifically the p43 mitochondrial T3 receptor. We found that these animals were hypermetabolic, hyperphagic, and displayed a down setting of the core body temperature. However, p43-/- animals do not present cold intolerance or defect of facultative thermogenesis. In addition, the mitochondrial function of BAT is slightly affected in the absence of p43. Our study, therefore, suggests a complementarity of action between the mitochondrial receptor and other proteins encoded by the Thra gene in the control of basal metabolism,facultative thermogenesis, and determination of the set point of temperature regulation
Analyse des risques psychosociaux et de la qualité de vie au travail. Diagnostic et préconisations (unité DMEM)
il s'agit d'un type de produit dont les métadonnées ne correspondent pas aux métadonnées attendues dans les autres types de produit : ACTIVITY_REPORTAnalyse des risques psychosociaux et de la qualité de vie au travail. Diagnostic et préconisations (unité DMEM
Analyse des risques psychosociaux et de la qualité de vie au travail. Diagnostic et préconisations (unité DMEM)
il s'agit d'un type de produit dont les métadonnées ne correspondent pas aux métadonnées attendues dans les autres types de produit : ACTIVITY_REPORTAnalyse des risques psychosociaux et de la qualité de vie au travail. Diagnostic et préconisations (unité DMEM
Role of mitochondrial and cytosolic isoforms of NAD+ dependent deacetylase SIRT3 in skeletal muscle homeostasis
Role of mitochondrial and cytosolic isoforms of NAD+ dependent deacetylase SIRT3 in skeletal muscle homeostasis. EUROMIT 2014, 9. International Meeting on Mitochondrial Patholog
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