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The mitochondrion as a primary site of action of glucocorticoids: the interaction of the glucocorticoid receptor with mitochondrial DNA sequences showing partial similarity to the nuclear glucocorticoid responsive elements
Abstract
Six mitochondrial genome sequences, showing strong similarity to the glucocorticoid responsive element consensus sequence (GRE), four localized within the cytochrome c oxidase (COX) subunit I and II genes (GREs I-IV) and two within the D-loop region (GREs a and b) have been examined as binding sites of glucocorticoid receptor (GR) from rat liver cytosol. Purified GR from rat liver cytosol binds with high specificity to all potential mitochondrial GREs, as shown by filter retention and gel shift assays. Specific binding of protein(s), present in a mitochondrial extract from dexamethasone-induced mice, to all six putative mitochondrial GREs was also documented by the same methodology. Both purified GR and protein(s) from mitochondrial extract give the same band in the gel retardation assay. Using monospecific anti-glucocorticoid receptor polyclonal antibody (EP), a supershift of the gel retarded protein-DNA band was obtained. These results demonstrate that the mitochondrial genome sequences examined have characteristics of GREs, since they show the capacity to specifically bind the respective receptor protein. These findings support the hypothesis that the mitochondrial genome is a primary site of action of steroid and thyroid hormones (Sekeris C.E.: The mitochondrial genome: a possible primary site of action of steroid hormones, In vivo 4 (1990) 317-320).
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“these elements have been found in mtDNA accompanied by oestrogen and androgen receptors (Demonacos et al., 1995; Demonacos et al., 1996).”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Demonacos et al., 1995
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Metadata
- Authors
- Demonacos, C., Djordjevic-Markovic, R., Tsawdaroglou, N., & Sekeris, C. E.
- Affiliations
- National Hellenic Research Foundation (GR)
- Corresponding author
- Sekeris, C.E.
- ORCID
- Demonacos, C.
- Venue
- The Journal of Steroid Biochemistry and Molecular Biology
- Publisher
- Elsevier BV
- Published
- 1995-10
- Volume
- 55
- Issue
- 1
- Pages
- 43-55
- ISSN
- 0960-0760 (ISSN-L)
- OpenAlex
- W2047490631
- Cited by
- 131
- References
- 46
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 7 · 2021: 5 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 7 · 2015: 7 · 2014: 3 · 2013: 4 · 2012: 9
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- National Hellenic Research Foundation Helios Repository (National Hellenic Research Foundation) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- glucocorticoid receptor, mitochondria, mitochondrial DNA, glucocorticoid response element, cytochrome c oxidase subunit I, cytochrome c oxidase subunit II, D-loop, dexamethasone, steroid hormone action, receptor-DNA binding, rat liver
- MeSH terms
- Animals, Base Sequence, Binding Sites, Binding, Competitive, Electron Transport Complex IV, Cytosol, Dexamethasone, DNA-Binding Proteins, DNA, Mitochondrial, Male, Mice, Inbred BALB C, Mitochondria, Liver, Molecular Sequence Data, Oligodeoxyribonucleotides, Receptors, Glucocorticoid, Regulatory Sequences, Nucleic Acid, Sequence Homology, Nucleic Acid, Consensus Sequence, Rats, Wistar, Mice, Rats
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