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Mitochondrial localization of ERα and ERβ in human MCF7 cells
Abstract
We observed previously that estrogen treatment increased the transcript levels of several mitochondrial DNA (mtDNA)-encoded genes for mitochondrial respiratory chain (MRC) proteins and MRC activity in rat hepatocytes and human Hep G2 cells. Others have reported detection of estrogen receptors (ER), ERalpha and ERbeta, in mitochondria of rabbit ovarian and uterine tissue. In this study, we have extended these observations. Using cellular fractionation and Western blot with ERalpha- and ERbeta-specific antibodies, we observed that ERalpha and ERbeta are present in mitochondria of human MCF7 cells and that the mitochondrial ERalpha and ERbeta account for 10 and 18%, respectively, of total cellular ERalpha and ERbeta in 17beta-estradiol (E(2))-treated MCF7 cells. We also found that E(2) significantly enhanced the amounts of mitochondrial ERalpha and ERbeta in a time- and concentration-dependent manner and that these effects are accompanied by a significant increase in the transcript levels of mtDNA-encoded genes, i.e., cytochrome c oxidase subunits I and II. Moreover, we demonstrated that these E(2)-mediated effects were inhibited by the pure ER antagonist, ICI-182780, indicating the involvement of ERs. Using immunohistochemistry with confocal microscopy and immunogold electron microscopy, we demonstrated that ERalpha and ERbeta are located within the MCF7 cell mitochondrial matrix. Computer analysis identified a putative internal mitochondrial targeting peptide signal within human ERbeta, suggesting an inherent potential for ERbeta to enter mitochondria. These findings confirm the observations of others and provide additional support for this novel localization of the ERs and for a potentially important role of the ER in the regulation of mtDNA transcription.
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“Interestingly, it was found that subpopulations of ERα and ERβ exist in mitochondria, although it is still unclear if they can directly regulate mtDNA transcription (132–134).”
From From mitochondria to sarcopenia: role of 17β-estradiol and testosterone (2023) · cites this paper as [132]
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Metadata
- Authors
- Chen, J. Q., Delannoy, M., Cooke, C., & Yager, J. D.
- Affiliations
- Johns Hopkins University (US)
- ORCID
- Delannoy, Michael
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2004-06
- Volume
- 286
- Issue
- 6
- Pages
- E1011-E1022
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2136888738
- Cited by
- 272
- References
- 78
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 7 · 2023: 6 · 2022: 5 · 2021: 9 · 2020: 7 · 2019: 8 · 2018: 13 · 2017: 12 · 2016: 13 · 2015: 13 · 2014: 13 · 2013: 11 · 2012: 19
- FWCI
- 9.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA 36701, CA 77550, R01CA036701, R01CA077550)
- National Institute of Environmental Health Sciences (P30 ES03819, P30ES003819)
- 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
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- estrogen receptor alpha, estrogen receptor beta, mitochondrial localization, MCF-7 cells, estradiol, mitochondrial respiratory chain, fulvestrant, mitochondrial targeting peptide, mitochondrial matrix
- MeSH terms
- Fulvestrant, Antibody Specificity, Breast Neoplasms, Cell Nucleus, DNA, Mitochondrial, Estradiol, Estrogen Antagonists, Humans, Immunohistochemistry, Mitochondria, Receptors, Estrogen, Subcellular Fractions, Transcription, Genetic, Gene Expression, Microscopy, Immunoelectron, Microscopy, Confocal, Protein Sorting Signals, Cell Line, Tumor, Estrogen Receptor alpha, Estrogen Receptor beta
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