Cited by 272Estrogen and related hormone effectsMitochondrial Function and PathologyAdipose Tissue and Metabolism

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Mitochondrial localization of ERα and ERβ in human MCF7 cells

Chen, Jin Q., Delannoy, Michael, Cooke, Carol, Yager, James D.·2004·American Journal of Physiology-Endocrinology and Metabolism

DOI 10.1152/ajpendo.00508.2003

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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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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
DOI: 10.1152/ajpendo.00508.2003
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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Mitochondrial localization of ERα and ERβ in human MCF7 cells

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