Estrogen-Mediated Regulation of Mitochondrial Gene Expression

Estrogens, in particular 17β-estradiol, are well-known regulators of essential cellular functions; however, discrepancies remain over the mechanisms by which they act on mitochondria. Here we propose a novel mechanism for the direct regulation of mitochondrial gene expression by estrogen under metab...

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Bibliographic Details
Published in:Molecular endocrinology (Baltimore, Md.) Md.), 2015-01, Vol.29 (1), p.14-27
Main Authors: Lopez Sanchez, Maria I. G, Shearwood, Anne-Marie J, Chia, Tiongsun, Davies, Stefan M. K, Rackham, Oliver, Filipovska, Aleksandra
Format: Article
Language:English
Subjects:
3-Hydroxyacyl CoA Dehydrogenases - biosynthesis
3-Hydroxyacyl CoA Dehydrogenases - genetics
3-Hydroxyacyl CoA Dehydrogenases - metabolism
Cell Line, Tumor
Estradiol - metabolism
Estrogen Receptor alpha - biosynthesis
Estrogen Receptor alpha - genetics
Estrogen Receptor alpha - metabolism
Estrogens - metabolism
Gene Expression Regulation - genetics
Genes, Mitochondrial - genetics
Humans
MCF-7 Cells
Mitochondria - enzymology
Mitochondria - genetics
Mitochondria - metabolism
Original Research
RNA Interference
RNA, Small Interfering
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Summary:Estrogens, in particular 17β-estradiol, are well-known regulators of essential cellular functions; however, discrepancies remain over the mechanisms by which they act on mitochondria. Here we propose a novel mechanism for the direct regulation of mitochondrial gene expression by estrogen under metabolic stress. We show that in serum-depleted medium, estrogen stimulates a rapid relocation of estrogen receptor-α to mitochondria, in which it elicits a cellular response, resulting in an increase in mitochondrial RNA abundance. Mitochondrial RNA levels are regulated through the association of estrogen receptor-α with 17β-hydroxysteroid dehydrogenase 10, a multifunctional protein involved in steroid metabolism that is also a core subunit of the mitochondrial ribonuclease P complex responsible for the cleavage of mitochondrial polycistronic transcripts. Processing of mitochondrial transcripts affects mitochondrial gene expression by controlling the levels of mature RNAs available for translation. This work provides the first mechanism linking RNA processing and estrogen activation in mitochondrial gene expression and underscores the coordinated response between the nucleus and mitochondria in response to stress.
ISSN:0888-8809
1944-9917
DOI:10.1210/me.2014-1077