The mitochondrion as a primary site of action of steroid and thyroid hormones: Presence and action of steroid and thyroid hormone receptors in mitochondria of animal cells

Psarra, Anna‐Maria G.; Solakidi, Sylvia; Sékeris, Constantin E.

doi:10.1016/j.mce.2005.11.025

Cited by 137 publications

(100 citation statements)

References 89 publications

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“…Interestingly, GR binding to mtDNA was maximal at the 300-μg/kg dose but was lower at the 3 mg/kg dose, suggesting the descending limb of the inverted-U doseresponse relationship often observed with corticosteroids (22). Furthermore, the GR binding or interaction site we describe coincides closely with the GRα GRE identified previously by the Sekeris laboratory in human cell lines and mouse hepatocytes (14,19). It is worth noting that, although our ChIP-Seq data show an interaction with a putative GRE, the method does not demonstrate that a direct GR-DNA binding event has occurred, because other elements of the transcriptional machinery may be involved.…”

Section: Discussionsupporting

confidence: 81%

“…5). ND-3 and ATP-6 also are relatively close to GREs (14). Although we did not observe significant GR interaction with the presumptive GRE near ND-3 and ATP-6, such interaction may have occurred at an earlier time point than was captured in our ChIP-seq analysis.…”

Section: Discussioncontrasting

confidence: 57%

“…It has been demonstrated previously that stress and corticosteroids induce translocation of the GR into brain mitochondria and that this translocation alters mitochondrial physiology (15). The GR is a well-described ligand-activated nuclear transcription factor, and the mtDNA contains GREs that can regulate mtDNA transcription in cultured human cell lines (13,14). These observations and the fact that GR translocates to the mitochondria in response to treatment with its endogenous ligand suggested that it might regulate transcription of the brain mitochondrial genome as well.…”

Section: Discussionmentioning

confidence: 99%

“…Steroid hormone receptors, including estrogen receptors and GRs, translocate into brain mitochondria. Studies in cultured cells suggest that mtDNA contains GC response elements (GREs) and that these may have a functional role in regulating mtDNA transcription (13)(14)(15)(16)(17)(18). In both cultured neurons and in prefrontal cortex tissue, GC treatment showed a biphasic effect on mitochondrial oxidation, membrane potential, and calcium capacity, with lower doses improving these measures and higher or chronic doses and treatments causing deficits.…”

mentioning

confidence: 99%

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Stress and corticosteroids regulate rat hippocampal mitochondrial DNA gene expression via the glucocorticoid receptor

Hunter

Seligsohn

Rubin

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

134

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Glucocorticoids (GCs) are involved in stress and circadian regulation, and produce many actions via the GC receptor (GR), which is classically understood to function as a nuclear transcription factor. However, the nuclear genome is not the only genome in eukaryotic cells. The mitochondria also contain a small circular genome, the mitochondrial DNA (mtDNA), that encodes 13 polypeptides. Recent work has established that, in the brain and other systems, the GR is translocated from the cytosol to the mitochondria and that stress and corticosteroids have a direct influence on mtDNA transcription and mitochondrial physiology. To determine if stress affects mitochondrially transcribed mRNA (mtRNA) expression, we exposed adult male rats to both acute and chronic immobilization stress and examined mtRNA expression using quantitative RT-PCR. We found that acute stress had a main effect on mtRNA expression and that expression of NADH dehydrogenase 1, 3, and 6 (ND-1, ND-3, ND-6) and ATP synthase 6 (ATP-6) genes was significantly down-regulated. Chronic stress induced a significant up-regulation of ND-6 expression. Adrenalectomy abolished acute stress-induced mtRNA regulation, demonstrating GC dependence. ChIP sequencing of GR showed that corticosterone treatment induced a dose-dependent association of the GR with the control region of the mitochondrial genome. These findings demonstrate GR and stress-dependent transcriptional regulation of the mitochondrial genome in vivo and are consistent with previous work linking stress and GCs with changes in the function of brain mitochondria.nuclear receptors | allostasis | mitochondrial plasticity | brain metabolism | mitochondrial transcription

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Section: Discussionsupporting

confidence: 81%

Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Stress and corticosteroids regulate rat hippocampal mitochondrial DNA gene expression via the glucocorticoid receptor

Hunter

Seligsohn

Rubin

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

134

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“…Available online September 16, 2011. Published October 10, 2011 Thyroid hormone (TH) is known to modulate developmental and metabolic processes by interacting with specific binding sites located in the nucleus, cytoplasm, organelles, and plasma membrane (1)(2)(3)(4)(5). It is well known that TH affects the metabolic rate by controlling lipid, protein and carbohydrate synthesis and degradation (6,7), actions that are also shared by insulin and growth hormone (GH) (8)(9)(10)(11).…”

mentioning

confidence: 99%

Hypothyroidism decreases proinsulin gene expression and the attachment of its mRNA and eEF1A protein to the actin cytoskeleton of INS-1E cells

Goulart-Silva

Serrano‐Nascimento

Nunes

2011

Braz J Med Biol Res

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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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The mitochondrion as a primary site of action of steroid and thyroid hormones: Presence and action of steroid and thyroid hormone receptors in mitochondria of animal cells

Cited by 137 publications

References 89 publications

Stress and corticosteroids regulate rat hippocampal mitochondrial DNA gene expression via the glucocorticoid receptor

Stress and corticosteroids regulate rat hippocampal mitochondrial DNA gene expression via the glucocorticoid receptor

Hypothyroidism decreases proinsulin gene expression and the attachment of its mRNA and eEF1A protein to the actin cytoskeleton of INS-1E cells

Steroid and thyroid hormone receptors in mitochondria

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