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 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.
Harry Perkins Institute of Medical Research and Centre for Medical Research (M.I.G.L.S., A.-M.J.S., T.-S.C., S.M.K.D., O.R., A.F.), Queen Elizabeth II Medical Centre, Nedlands, and School of Chemistry and Biochemistry (O.R., A.F.), The University of Western Australia, Crawley, Western Australia 6009, Australia.
Maria I G Lopez
MI
Sanchez
Anne-Marie J
AM
Shearwood
Tiongsun
T
Chia
Stefan M K
SM
Davies
Oliver
O
Rackham
Aleksandra
A
Filipovska
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D050259:Genes, Mitochondrial / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D034741:RNA, Small Interfering; D004958:Estradiol; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human