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Estrogens regulate life and death in mitochondria

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Abstract

Estrogens coordinate and integrate cellular metabolism and mitochondrial activities by direct and indirect mechanisms mediated by differential expression and localization of estrogen receptors (ER) in a cell-specific manner. Estrogens regulate transcription and cell signaling pathways that converge to stimulate mitochondrial function- including mitochondrial bioenergetics, mitochondrial fusion and fission, calcium homeostasis, and antioxidant defense against free radicals. Estrogens regulate nuclear gene transcription by binding and activating the classical genomic estrogen receptors α and β (ERα and ERβ) and by activating plasma membrane-associated mERα, mERβ, and G-protein coupled ER (GPER, GPER1). Localization of ERα and ERβ within mitochondria and in the mitochondrial membrane provides additional mechanisms of regulation. Here we review the mechanisms of rapid and longer-term effects of estrogens and selective ER modulators (SERMs, e.g., tamoxifen (TAM)) on mitochondrial biogenesis, morphology, and function including regulation of Nuclear Respiratory Factor-1 (NRF-1, NRF1) transcription. NRF-1 is a nuclear transcription factor that promotes transcription of mitochondrial transcription factor TFAM (mtDNA maintenance factorFA) which then regulates mtDNA-encoded genes. The nuclear effects of estrogens on gene expression directly controlling mitochondrial biogenesis, oxygen consumption, mtDNA transcription, and apoptosis are reviewed.

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References

  • Anbalagan M, Rowan BG (2015) Estrogen receptor alpha phosphorylation and its functional impact in human breast cancer. Mol Cell Endocrinol 418, Part 3:264–272 doi: 10.1016/j.mce.2015.01.016

  • Ariazi EA et al. (2011) Estrogen induces apoptosis in estrogen deprivation-resistant breast cancer through stress responses as identified by global gene expression across time Proceedings of the National Academy of Sciences 108:18879-18886 doi:10.1073/pnas.1115188108

  • Arnold S, de Araújo GW, Beyer C (2008) Gender-specific regulation of mitochondrial fusion and fission gene transcription and viability of cortical astrocytes by steroid hormones. J Mol Endocrinol 41:289–300. doi:10.1677/jme-08-0085

    Article  CAS  Google Scholar 

  • Bao L, Zhou S, Zhao H, Zu J, He Q, Ye X, Cui G (2015) Neuroprotective Effects of 17beta-Estradiol against Thrombin-Induced Apoptosis in Primary Cultured Cortical Neurons. Pharmacology 96:284–289. doi:10.1159/000440961

    Article  CAS  Google Scholar 

  • Barton M, Prossnitz ER (2015) Emerging roles of GPER in diabetes and atherosclerosis. Trends Endocrinol Metab 26:185–192. doi:10.1016/j.tem.2015.02.003

    Article  CAS  Google Scholar 

  • Belcredito S, Brusadelli A, Maggi A (2000) Estrogens, apoptosis and cells of neural origin. J Neurocytol 29:359–365

    Article  CAS  Google Scholar 

  • Bohl C, Harihar S, Denning W, Sharma R, Welch D (2014) Metastasis suppressors in breast cancers: mechanistic insights and clinical potential. J Mol Med 92:13–30. doi:10.1007/s00109-013-1109-y

    Article  CAS  Google Scholar 

  • Bondesson M, Hao R, Lin CY, Williams C, Gustafsson JA (2014) Estrogen receptor signaling during vertebrate development. Biochim Biophys Acta. doi:10.1016/j.bbagrm.2014.06.005

    Google Scholar 

  • Borengasser SJ, Faske J, Kang P, Blackburn ML, Badger TM, Shankar K (2014) In utero exposure to prepregnancy maternal obesity and postweaning high-fat diet impair regulators of mitochondrial dynamics in rat placenta and offspring. Physiol Genomics 46:841–850

    Article  CAS  Google Scholar 

  • Borras C, Gambini J, Gomez-Cabrera MC, Sastre J, Pallardo FV, Mann GE, Vina J (2006) Genistein, a soy isoflavone, up-regulates expression of antioxidant genes: involvement of estrogen receptors, ERK1/2, and NF{kappa}B. FASEB J 20:2136–2138. doi:10.1096/fj.05-5522fje

    Article  CAS  Google Scholar 

  • Cam H et al (2004) A Common Set of Gene Regulatory Networks Links Metabolism and Growth Inhibition. Mol Cell 16:399–411

    Article  CAS  Google Scholar 

  • Capllonch-Amer G, Sbert-Roig M, Galmes-Pascual BM, Proenza AM, Llado I, Gianotti M, Garcia-Palmer FJ (2014) Estradiol stimulates mitochondrial biogenesis and adiponectin expression in skeletal muscle. J Endocrinol 221:391–403. doi:10.1530/joe-14-0008

    Article  CAS  Google Scholar 

  • Carroll JS et al (2005) Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein. FoxA1. Cell 122:33–43

    Article  CAS  Google Scholar 

  • Carson JA, Manolagas SC (2015) Effects of sex steroids on bones and muscles: Similarities, parallels, and putative interactions in health and disease. Bone 80:67–78. doi:10.1016/j.bone.2015.04.015

    Article  CAS  Google Scholar 

  • Chambliss KL, Simon L, Yuhanna IS, Mineo C, Shaul PW (2005) Dissecting the basis of nongenomic activation of endothelial nitric oxide synthase by estradiol: role of ERalpha domains with known nuclear functions. Mol Endocrinol 19:277–289

    Article  CAS  Google Scholar 

  • Chen J-Q, Yager JD, Russo J (2005) Regulation of mitochondrial respiratory chain structure and function by estrogens/estrogen receptors and potential physiological/pathophysiological implications. Biochim. Biophys. Acta (BBA) (BBA) – Mol Cell Res 1746:1–17

    Article  CAS  Google Scholar 

  • Chen JQ, Brown TR, Yager JD (2008) Mechanisms of hormone carcinogenesis: evolution of views, role of mitochondria. Adv Exp Med Biol 630:1–18

    Article  CAS  Google Scholar 

  • Chen J-Q, Cammarata PR, Baines CP, Yager JD (2009) Regulation of mitochondrial respiratory chain biogenesis by estrogens/estrogen receptors and physiological, pathological and pharmacological implications. Biochim Biophys Acta Biomembr - Mol Cell Res 1793:1540–1570

    Article  CAS  Google Scholar 

  • Chen Y et al (2015) 17β-estradiol prevents cardiac diastolic dysfunction by stimulating mitochondrial function: A preclinical study in a mouse model of a human hypertrophic cardiomyopathy mutation. J Steroid Biochem Mol Biol 147:92–102. doi:10.1016/j.jsbmb.2014.12.011

    Article  CAS  Google Scholar 

  • Cheng C-T et al. (2016) Metabolic stress-induced phosphorylation of KAP1 Ser473 blocks mitochondrial fusion in breast cancer cells. Cancer Res

    Google Scholar 

  • Conner P (2007) Breast response to menopausal hormone therapy--aspects on proliferation, apoptosis and mammographic density. Ann Med 39:28–41

    Article  CAS  Google Scholar 

  • Cruz P, Epunan MJ, Ramirez ME, Torres CG, Valladares LE, Sierralta WD (2012) 27-hydroxycholesterol and the expression of three estrogen-sensitive proteins in MCF7 cells. Oncol Rep 28:992–998. doi:10.3892/or.2012.1859

    Article  CAS  Google Scholar 

  • de Oliveira MR (2016) Evidence for genistein as a mitochondriotropic molecule. Mitochondrion 29:35–44. doi:10.1016/j.mito.2016.05.005

    Article  CAS  Google Scholar 

  • Deblois G et al (2009) Genome-Wide Identification of Direct Target Genes Implicates Estrogen-Related Receptor {alpha} as a Determinant of Breast Cancer Heterogeneity. Cancer Res 69:6149–6157. doi:10.1158/0008-5472.can-09-1251

    Article  CAS  Google Scholar 

  • Deroo BJ, Hewitt SC, Collins JB, Grissom SF, Hamilton KJ, Korach KS (2009) Profile of estrogen-responsive genes in an estrogen-specific mammary gland outgrowth model. Mol Reprod Dev 76:733–750. doi:10.1002/mrd.21041

    Article  CAS  Google Scholar 

  • DuSell CD, Umetani M, Shaul PW, Mangelsdorf DJ, McDonnell DP (2008) 27-Hydroxycholesterol Is an Endogenous Selective Estrogen Receptor Modulator. Mol Endocrinol 22:65–77. doi:10.1210/me.2007-0383

    Article  CAS  Google Scholar 

  • Elangovan S et al (2011) SIRT1 Is Essential for Oncogenic Signaling by Estrogen/Estrogen Receptor α in Breast Cancer. Cancer Res 71:6654–6664. doi:10.1158/0008-5472.can-11-1446

    Article  CAS  Google Scholar 

  • Felty Q, Xiong WC, Sun D, Sarkar S, Singh KP, Parkash J, Roy D (2005) Estrogen-induced mitochondrial reactive oxygen species as signal-transducing messengers. Biochemistry (Mosc) 44:6900–6909

    Article  CAS  Google Scholar 

  • Filardo EJ, Thomas P (2012) Minireview: G Protein-Coupled Estrogen Receptor-1, GPER-1: Its Mechanism of Action and Role in Female Reproductive Cancer, Renal and Vascular Physiology. Endocrinology 153:2953–2962. doi:10.1210/en.2012-1061

    Article  CAS  Google Scholar 

  • Finck BN, Kelly DP (2006) PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. J Clin Invest 116:615–622. doi:10.1172/jci27794

    Article  CAS  Google Scholar 

  • Finck BN, Kelly DP (2007) Peroxisome Proliferator-Activated Receptor {gamma} Coactivator-1 (PGC-1) Regulatory Cascade in Cardiac Physiology and Disease. Circulation 115:2540–2548. doi:10.1161/circulationaha.107.670588

    Article  Google Scholar 

  • Flach KD, Zwart W (2016) The first decade of estrogen receptor cistromics in breast cancer. J Endocrinol 229:R43–R56. doi:10.1530/joe-16-0003

    Article  CAS  Google Scholar 

  • Fong CJ, Burgoon LD, Williams KJ, Forgacs AL, Zacharewski TR (2007) Comparative temporal and dose-dependent morphological and transcriptional uterine effects elicited by tamoxifen and ethynylestradiol in immature, ovariectomized mice. BMC Genomics 8:151

    Article  CAS  Google Scholar 

  • Fong CJ, Burgoon LD, Williams KJ, Jones AD, Forgacs AL, Zacharewski TR (2010) Effects of tamoxifen and ethynylestradiol cotreatment on uterine gene expression in immature, ovariectomized mice. J Mol Endocrinol 45:161–173. doi:10.1677/jme-09-0158

    Article  CAS  Google Scholar 

  • Fujisawa K et al (2009) TZDs reduce mitochondrial ROS production and enhance mitochondrial biogenesis. Biochem Biophys Res Commun 379:43–48. doi:10.1016/j.bbrc.2008.11.141

    Article  CAS  Google Scholar 

  • Gaudet HM, Cheng SB, Christensen EM, Filardo EJ (2015) The G-protein-coupled estrogen receptor, GPER: the inside and inside-out story. Mol Cell Endocrinol 418(3):207–219. doi:10.1016/j.mce.2015.07.016

  • Germain D (2016) Chapter Five - Sirtuins and the Estrogen Receptor as Regulators of the Mammalian Mitochondrial UPR in Cancer and Aging. In: Kenneth DT, Paul BF (eds) Advances in Cancer Research, Volume 130. Academic Press, pp 211-256. Doi: 10.1016/bs.acr.2016.01.004

  • Grimm A, Schmitt K, Lang UE, Mensah-Nyagan AG, Eckert A (2014) Improvement of neuronal bioenergetics by neurosteroids: Implications for age-related neurodegenerative disorders Biochimica et. Biophysica Acta (BBA) - Molecular Basis of Disease 1842:2427–2438. doi:10.1016/j.bbadis.2014.09.013

    Article  CAS  Google Scholar 

  • Grober O et al (2011) Global analysis of estrogen receptor beta binding to breast cancer cell genome reveals an extensive interplay with estrogen receptor alpha for target gene regulation. BMC Genomics 12:36

    Article  CAS  Google Scholar 

  • Guarente L (2008) Mitochondria--A Nexus for Aging, Calorie Restriction, and Sirtuins? Cell 132:171–176

    Article  CAS  Google Scholar 

  • Gugneja S, Virbasius CM, Scarpulla RC (1996) Nuclear respiratory factors 1 and 2 utilize similar glutamine- containing clusters of hydrophobic residues to activate transcription. Mol Cell Biol 16:5708–5716

    Article  CAS  Google Scholar 

  • Guha M, Avadhani NG (2013) Mitochondrial retrograde signaling at the crossroads of tumor bioenergetics, genetics and epigenetics. Mitochondrion 13:577–591. doi:10.1016/j.mito.2013.08.007

    Article  CAS  Google Scholar 

  • Gurd BJ (2011) Deacetylation of PGC-1alpha by SIRT1: importance for skeletal muscle function and exercise-induced mitochondrial biogenesis. Appl Physiol Nutr Metab 36:589–597. doi:10.1139/h11-070

    Article  CAS  Google Scholar 

  • Gustafsson J-A (2016) Historical overview of nuclear receptors. J Steroid Biochem Mol Biol 157:3–6. doi:10.1016/j.jsbmb.2015.03.004

    Article  CAS  Google Scholar 

  • Gustafsson KL et al (2016) The role of membrane ERalpha signaling in bone and other major estrogen responsive tissues. Sci Reports 6:29473. doi:10.1038/srep29473

    Article  CAS  Google Scholar 

  • Hara Y, Waters EM, McEwen BS, Morrison JH (2015) Estrogen Effects on Cognitive and Synaptic Health Over the Lifecourse. Physiol Rev 95:785–807

    Article  CAS  Google Scholar 

  • Hewitt SC et al (2012) Research Resource: Whole-Genome Estrogen Receptor α Binding in Mouse Uterine Tissue Revealed by ChIP-Seq. Mol Endocrinol 26:887–898. doi:10.1210/me.2011-1311

    Article  CAS  Google Scholar 

  • Holmes KA et al (2012) Transducin-like enhancer protein 1 mediates estrogen receptor binding and transcriptional activity in breast cancer cells. Proc Natl Acad Sci 109:2748–2753. doi:10.1073/pnas.1018863108

    Article  CAS  Google Scholar 

  • Horan MP, Cooper DN (2014) The emergence of the mitochondrial genome as a partial regulator of nuclear function is providing new insights into the genetic mechanisms underlying age-related complex disease. Hum Genet 133:435–458. doi:10.1007/s00439-013-1402-4

    Article  CAS  Google Scholar 

  • Hossain MB, Ji P, Anish R, Jacobson RH, Takada S (2009) Poly(ADP-ribose) Polymerase 1 Interacts with Nuclear Respiratory Factor 1 (NRF-1) and Plays a Role in NRF-1 Transcriptional Regulation. J Biol Chem 284:8621–8632. doi:10.1074/jbc.M807198200

    Article  CAS  Google Scholar 

  • Huo L, Scarpulla RC (2001) Mitochondrial DNA Instability and Peri-Implantation Lethality Associated with Targeted Disruption of Nuclear Respiratory Factor 1 in Mice. Mol Cell Biol 21:644–654

    Article  CAS  Google Scholar 

  • Irwin RW, Yao J, Ahmed SS, Hamilton RT, Cadenas E, Brinton RD (2011) Medroxyprogesterone Acetate Antagonizes Estrogen Up-Regulation of Brain Mitochondrial Function. Endocrinology 152:556–567. doi:10.1210/en.2010-1061

    Article  CAS  Google Scholar 

  • Irwin RW, Yao J, To J, Hamilton RT, Cadenas E, Brinton RD (2012) Selective Oestrogen Receptor Modulators Differentially Potentiate Brain Mitochondrial Function. J Neuroendocrinol 24:236–248. doi:10.1111/j.1365-2826.2011.02251.x

    Article  CAS  Google Scholar 

  • Ivanova MM et al (2011) Tamoxifen increases nuclear respiratory factor 1 transcription by activating estrogen receptor β and AP-1 recruitment to adjacent promoter binding sites. FASEB J 25:1402–1416. doi:10.1096/fj.10-169029

    Article  CAS  Google Scholar 

  • Ivanova MM, Radde BN, Son J, Mehta FF, Chung S-H, Klinge CM (2013) Estradiol and tamoxifen regulate NRF-1 and mitochondrial function in mouse mammary gland and uterus. J Mol Endocrinol 51:233–246. doi:10.1530/jme-13-0051

    Article  CAS  Google Scholar 

  • Iwafuchi-Doi M, Zaret KS (2014) Pioneer transcription factors in cell reprogramming. Genes Dev 28:2679–2692. doi:10.1101/gad.253443.114

    Article  CAS  Google Scholar 

  • Jia G, Aroor AR, Sowers JR (2014) Chapter Nine - Estrogen and Mitochondria Function in Cardiorenal Metabolic Syndrome. In: Heinz DO (ed) Progress in Molecular Biology and Translational Science, vol Volume 127. Academic Press, pp 229-249. Doi: 10.1016/B978-0-12-394625-6.00009-X

  • Jin-Qiang C, Yager JD (2004) Estrogen's Effects on Mitochondrial Gene Expression: Mechanisms and Potential Contributions to Estrogen Carcinogenesis. Ann N Y Acad Sci 1028:258–272

    Article  CAS  Google Scholar 

  • Jordan VC (2015) The new biology of estrogen-induced apoptosis applied to treat and prevent breast cancer. Endocr Relat Cancer 22:R1–R31. doi:10.1530/erc-14-0448

    Article  CAS  Google Scholar 

  • Jovaisaite V, Mouchiroud L, Auwerx J (2013) The mitochondrial unfolded protein response, a conserved stress response pathway with implications in health and disease. J Exp Biol 217:137–143

    Article  CAS  Google Scholar 

  • Ju X, Wen Y, Metzger D, Jung M (2013) The role of p38 in mitochondrial respiration in male and female mice. Neurosci Lett 544:152–156. doi:10.1016/j.neulet.2013.04.004

    Article  CAS  Google Scholar 

  • Keller KM, Howlett SE (2016) Sex Differences in the Biology and Pathology of the Aging Heart. Can J Cardiol. doi:10.1016/j.cjca.2016.03.017

    Google Scholar 

  • Kelly DP, Scarpulla RC (2004) Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev 18:357–368

    Article  CAS  Google Scholar 

  • Kemper MF, Stirone C, Krause DN, Duckles SP, Procaccio V (2014) Genomic and non-genomic regulation of PGC1 isoforms by estrogen to increase cerebral vascular mitochondrial biogenesis and reactive oxygen species protection. Eur J Pharmacol 723:322–329. doi:10.1016/j.ejphar.2013.11.009

    Article  CAS  Google Scholar 

  • Klinge CM (2008) Estrogenic control of mitochondrial function and biogenesis. J Cell Biochem 105:1342–1351

    Article  CAS  Google Scholar 

  • Klinge CM (2012) miRNAs and estrogen action. Trends Endocrinol Metab 23:223–233. doi:10.1016/j.tem.2012.03.002

    Article  CAS  Google Scholar 

  • Klinge CM (2015) miRNAs regulated by estrogens, tamoxifen, and endocrine disruptors and their downstream gene targets. Mol Cell Endocrinol 418:273–297. doi:10.1016/j.mce.2015.01.035

    Article  CAS  Google Scholar 

  • Knowlton AA, Korzick DH (2014) Estrogen and the female heart. Mol Cell Endocrinol 389:31–39. doi:10.1016/j.mce.2014.01.002

    Article  CAS  Google Scholar 

  • Kuiper GG, Carlsson B, Grandien J, Enmark E, Haggblad J, Nilsson S, Gustafsson J-A (1997) Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors a and b. Endocrinology 138:863–870

    Article  CAS  Google Scholar 

  • Lane RK, Hilsabeck T, Rea SL (2015) The role of mitochondrial dysfunction in age-related diseases Biochimica et. Biochim Biophys Acta (BBA) - Bioenergetics 1847:1387–1400. doi:10.1016/j.bbabio.2015.05.021

    Article  CAS  Google Scholar 

  • Lannigan DA (2003) Estrogen receptor phosphorylation. Steroids 68:1–9

    Article  CAS  Google Scholar 

  • Lappano R, Pisano A, Maggiolini M (2014) GPER function in breast cancer: an overview. Front Endocrinol 5. doi:10.3389/fendo.2014.00066

  • Lavigne Matthieu D et al (2015) Composite macroH2A/NRF-1 Nucleosomes Suppress Noise and Generate Robustness in Gene Expression. Cell Rep 11:1090–1101. doi:10.1016/j.celrep.2015.04.022

    Article  CAS  Google Scholar 

  • Le Romancer M et al (2008) Regulation of Estrogen Rapid Signaling through Arginine Methylation by PRMT1. Mol Cell 31:212–221

    Article  CAS  Google Scholar 

  • Le Romancer M, Poulard C, Cohen P, Sentis S, Renoir JM, Corbo L (2011) Cracking the estrogen receptor's posttranslational code in breast tumors. Endocr Rev 32:597–622. doi:10.1210/er.2010-0016

    Article  CAS  Google Scholar 

  • Lee C-H et al (2011) Aberrant Cell Proliferation by Enhanced Mitochondrial Biogenesis via mtTFA in Arsenical Skin Cancers. Am J Pathol 178:2066–2076. doi:10.1016/j.ajpath.2011.01.056

    Article  CAS  Google Scholar 

  • Levin ER (2011) Minireview: Extranuclear Steroid Receptors: Roles in Modulation of Cell Functions. Mol Endocrinol 25:377–384. doi:10.1210/me.2010-0284

    Article  CAS  Google Scholar 

  • Li L, Haynes MP, Bender JR (2003) Plasma membrane localization and function of the estrogen receptor alpha variant (ER46) in human endothelial cells. Proc Natl Acad Sci U S A 100:4807–4812

    Article  CAS  Google Scholar 

  • Li L et al (2007) Variant estrogen receptor c-Src molecular interdependence and c-Src structural requirements for endothelial NO synthase activation. Proc Natl Acad Sci 104:16468–16473. doi:10.1073/pnas.0704315104

    Article  CAS  Google Scholar 

  • Li W et al (2013) Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Nature 498:516–520. doi:10.1038/nature12210

    Article  CAS  Google Scholar 

  • Li W et al (2015) Condensin I and II Complexes License Full Estrogen Receptor α-Dependent Enhancer Activation. Mol Cell 59:188–202. doi:10.1016/j.molcel.2015.06.002

    Article  CAS  Google Scholar 

  • Liang J, Xie Q, Li P, Zhong X, Chen Y (2015) Mitochondrial estrogen receptor beta inhibits cell apoptosis via interaction with Bad in a ligand-independent manner. Mol Cell Biochem 401:71–86. doi:10.1007/s11010-014-2293-y

    Article  CAS  Google Scholar 

  • Liu W et al (2014a) Metastasis Suppressor KISS1 Seems to Reverse the Warburg Effect by Enhancing Mitochondrial Biogenesis. Cancer Res 74:954–963. doi:10.1158/0008-5472.can-13-1183

    Article  CAS  Google Scholar 

  • Liu Z et al (2014b) Enhancer Activation Requires trans-Recruitment of a Mega Transcription Factor Complex. Cell 159:358–373. doi:10.1016/j.cell.2014.08.027

    Article  CAS  Google Scholar 

  • Lonard DM, O'Malley BW (2012) Nuclear receptor coregulators: modulators of pathology and therapeutic targets. Nat Rev Endocrinol 8:598–604. doi:10.1038/nrendo.2012.100

    Article  CAS  Google Scholar 

  • Luo T, Kim JK (2016) The Role of Estrogen and Estrogen Receptors on Cardiomyocytes: An Overview Can. J Cardiol 32:1017–1025. doi:10.1016/j.cjca.2015.10.021

    Google Scholar 

  • Madak-Erdogan Z et al. (2016) Design of pathway preferential estrogens that provide beneficial metabolic and vascular effects without stimulating reproductive tissues. Science signaling 9:ra53-ra53

  • Magnani L, Lupien M (2014) Chromatin and epigenetic determinants of estrogen receptor alpha (ESR1) signaling. Mol Cell Endocrinol 382:633–641. doi:10.1016/j.mce.2013.04.026

    Article  CAS  Google Scholar 

  • Mahalingaiah PK, Ponnusamy L, Singh KP (2015) Chronic oxidative stress causes estrogen-independent aggressive phenotype, and epigenetic inactivation of estrogen receptor alpha in MCF-7 breast cancer cells. Breast Cancer Res Treat 153:41–56. doi:10.1007/s10549-015-3514-0

    Article  CAS  Google Scholar 

  • Mahmoodzadeh S et al (2014) Cardiomyocyte-specific Estrogen Receptor Alpha Increases Angiogenesis, Lymphangiogenesis and Reduces Fibrosis in the Female Mouse Heart Post-Myocardial Infarction. Journal Cell Sci and Ther 5:153. doi:10.4172/2157-7013.1000153

    Article  Google Scholar 

  • Mattingly KA, Klinge CM (2012) Diesel exhaust particulate extracts inhibit transcription of nuclear respiratory factor-1 and cell viability in human umbilical vein endothelial cells. Arch Toxicol 86:633–642. doi:10.1007/s00204-011-0778-y

    Article  CAS  Google Scholar 

  • Mattingly KA, Ivanova MM, Riggs KA, Wickramasinghe NS, Barch MJ, Klinge CM (2008) Estradiol stimulates transcription of Nuclear Respiratory Factor-1 and increases mitochondrial biogenesis. Mol Endocrinol 22:609–622. doi:10.1210/me.2007-0029

    Article  CAS  Google Scholar 

  • Michael Miller KK, Al-Rayyan N, Ivanova MM, Mattingly KA, Ripp SL, Klinge CM, Prough RA (2013) DHEA metabolites activate estrogen receptors alpha and beta. Steroids 78:15–25. doi:10.1016/j.steroids.2012.10.002

    Article  CAS  Google Scholar 

  • Milner TA, Lubbers LS, Alves SE, McEwen BS (2008) Nuclear and Extranuclear Estrogen Binding Sites in the Rat Forebrain and Autonomic Medullary Areas. Endocrinology 149:3306–3312. doi:10.1210/en.2008-0307

    Article  CAS  Google Scholar 

  • Mirebeau-Prunier D, Pennec SL, Jacques C, Gueguen N, Poirier J, Malthiery Y, Savagner F (2010) Estrogen-related receptor alpha and PGC-1-related coactivator constitute a novel complex mediating the biogenesis of functional mitochondria. FEBS J 277:713–725

    Article  CAS  Google Scholar 

  • Mishra P, Chan DC (2016) Metabolic regulation of mitochondrial dynamics. J Cell Biol 212:379–387. doi:10.1083/jcb.201511036

    Article  CAS  Google Scholar 

  • Misiak M, Beyer C, Arnold S (2010) Gender-specific role of mitochondria in the vulnerability of 6-hydroxydopamine-treated mesencephalic neurons Biochimica et. Biophysica Acta (BBA) - Bioenergetics 1797:1178–1188. doi:10.1016/j.bbabio.2010.04.009

    Article  CAS  Google Scholar 

  • Mo MS, Li HB, Wang BY, Wang SL, Zhu ZL, Yu XR (2013) PI3K/Akt and NF-κB activation following intravitreal administration of 17β-estradiol: Neuroprotection of the rat retina from light-induced apoptosis. Neuroscience 228:1–12. doi:10.1016/j.neuroscience.2012.10.002

    Article  CAS  Google Scholar 

  • Moggs JG et al (2004) Phenotypic anchoring of gene expression changes during estrogen-induced uterine growth. Environ Health Perspect 112:1589–1606

    Article  CAS  Google Scholar 

  • Monje P, Boland R (2001) Subcellular distribution of native estrogen receptor alpha and beta isoforms in rabbit uterus and ovary. J Cell Biochem 82:467–479

    Article  CAS  Google Scholar 

  • Moriarty K, Kim KH, Bender JR (2006) Estrogen Receptor-Mediated Rapid Signaling. Endocrinology 147:5557–5563. doi:10.1210/en.2006-0729

    Article  CAS  Google Scholar 

  • Morrill GA, Kostellow AB, Gupta RK (2015) Transmembrane helices in "classical" nuclear reproductive steroid receptors: a perspective. Nucl Recept Signal 13:e003. doi:10.1621/nrs.13003

    Google Scholar 

  • Nanjappa MK, Hess RA, Medrano TI, Locker SH, Levin ER, Cooke PS (2016) Membrane-Localized Estrogen Receptor 1 Is Required for Normal Male Reproductive Development and Function in Mice. Endocrinology 157:2909–2919. doi:10.1210/en.2016-1085

    Article  CAS  Google Scholar 

  • Nelson ER et al (2011) The Oxysterol, 27-Hydroxycholesterol, Links Cholesterol Metabolism to Bone Homeostasis Through Its Actions on the Estrogen and Liver X Receptors. Endocrinology 152:4691–4705. doi:10.1210/en.2011-1298

    Article  CAS  Google Scholar 

  • Nelson ER et al (2013) 27-Hydroxycholesterol Links Hypercholesterolemia and Breast Cancer Pathophysiology. Science 342:1094–1098. doi:10.1126/science.1241908

    Article  CAS  Google Scholar 

  • Nilsen J, Brinton RD (2003) Mechanism of estrogen-mediated neuroprotection: Regulation of mitochondrial calcium and Bcl-2 expression. Proc Natl Acad Sci U S A 100:2842–2847

    Article  CAS  Google Scholar 

  • Nilsen J, Brinton RD (2004) Mitochondria as therapeutic targets of estrogen action in the central nervous system. Curr Drug Targets CNS Neurol Disord 3:297–313

    Article  CAS  Google Scholar 

  • Notas G, Kampa M, Pelekanou V, Troullinaki M, Jacquot Y, Leclercq G, Castanas E (2013) Whole transcriptome analysis of the ERα synthetic fragment P295-T311 (ERα17p) identifies specific ERα-isoform (ERα, ERα36)-dependent and -independent actions in breast cancer cells. Mol Oncol 7:595–610. doi:10.1016/j.molonc.2013.02.012

    Article  CAS  Google Scholar 

  • Okoh VO et al (2015) Redox signalling to nuclear regulatory proteins by reactive oxygen species contributes to oestrogen-induced growth of breast cancer cells. Br J Cancer 112:1687–1702. doi:10.1038/bjc.2014.586

    Article  CAS  Google Scholar 

  • O'Lone R et al (2007) Estrogen Receptors {alpha} and {beta} Mediate Distinct Pathways of Vascular Gene Expression, Including Genes Involved in Mitochondrial Electron Transport and Generation of Reactive Oxygen Species. Mol Endocrinol 21:1281–1296. doi:10.1210/me.2006-0497

    Article  CAS  Google Scholar 

  • Pagliarini DJ et al (2008) A mitochondrial protein compendium elucidates complex I disease biology. Cell 134:112–123

    Article  CAS  Google Scholar 

  • Pang Y, Thomas P (2016) Additive effects of low concentrations of estradiol-17β and progesterone on nitric oxide production by human vascular endothelial cells through shared signaling pathways. J Steroid Biochem Mol Biol. doi:10.1016/j.jsbmb.2016.06.014

    Google Scholar 

  • Papa L, Germain D (2011) Estrogen receptor mediates a distinct mitochondrial unfolded protein response. J Cell Sci 124:1396–1402. doi:10.1242/jcs.078220

    Article  CAS  Google Scholar 

  • Pedram A, Razandi M, Levin ER (2006a) Nature of Functional Estrogen Receptors at the Plasma Membrane. Mol Endocrinol 20:1996–2009. doi:10.1210/me.2005-0525

    Article  CAS  Google Scholar 

  • Pedram A, Razandi M, Wallace DC, Levin ER (2006b) Functional Estrogen Receptors in the Mitochondria of Breast Cancer Cells. Mol Biol Cell 17:2125–2137

    Article  CAS  Google Scholar 

  • Pedram A, Razandi M, Kim JK, O'Mahony F, Lee EY, Luderer U, Levin ER (2009) Developmental Phenotype of a Membrane Only Estrogen Receptor {alpha} (MOER) Mouse. J Biol Chem 284:3488–3495. doi:10.1074/jbc.M806249200

    Article  CAS  Google Scholar 

  • Pedram A, Razandi M, Lewis M, Hammes S, Levin Ellis R (2014) Membrane-Localized Estrogen Receptor α Is Required for Normal Organ Development and Function. Dev Cell 29:482–490. doi:10.1016/j.devcel.2014.04.016

    Article  CAS  Google Scholar 

  • Pedram A, Razandi M, Blumberg B, Levin ER (2016) Membrane and nuclear estrogen receptor α collaborate to suppress adipogenesis but not triglyceride content. FASEB J 30:230–240. doi:10.1096/fj.15-274878

    Article  CAS  Google Scholar 

  • Penney RB, Roy D (2013) Thioredoxin-mediated redox regulation of resistance to endocrine therapy in breast cancer Biochimica et. Biophysica Acta (BBA) – Reviews Cancer 1836:60–79. doi:10.1186/1471-2164-9-239

    Article  CAS  Google Scholar 

  • Perillo B, Sasso A, Abbondanza C, Palumbo G (2000) 17beta -Estradiol Inhibits Apoptosis in MCF-7 Cells, Inducing bcl-2 Expression via Two Estrogen-Responsive Elements Present in the Coding Sequence. Mol Cell Biol 20:2890–2901

    Article  CAS  Google Scholar 

  • Piantadosi CA, Suliman HB (2006) Mitochondrial Transcription Factor A Induction by Redox Activation of Nuclear Respiratory Factor 1. J Biol Chem 281:324–333

    Article  CAS  Google Scholar 

  • Pietras RJ, Marquez-Garban DC (2007) Membrane-Associated Estrogen Receptor Signaling Pathways in Human Cancers. Clin Cancer Res 13:4672–4676. doi:10.1158/1078-0432.ccr-07-1373

    Article  CAS  Google Scholar 

  • Plenchette S, Romagny S, Laurens V, Bettaieb A (2015) S-nitrosylation in TNF superfamily signaling pathway: Implication in cancer. Redox Biol 6:507–515. doi:10.1016/j.redox.2015.08.019

    Article  CAS  Google Scholar 

  • Poulard C, Rambaud J, Hussein N, Corbo L, Le Romancer M (2014) JMJD6 Regulates ERα Methylation on Arginine. PLoS One 9:e87982. doi:10.1371/journal.pone.0087982

    Article  CAS  Google Scholar 

  • Prossnitz ER, Barton M (2014) Estrogen biology: New insights into GPER function and clinical opportunities. Mol Cell Endocrinol 389:71–83. doi:10.1016/j.mce.2014.02.002

    Article  CAS  Google Scholar 

  • Prossnitz ER, Hathaway HJ (2015) What have we learned about GPER function in physiology and disease from knockout mice? J Steroid Biochem Mol Biol 153:114–126. doi:10.1016/j.jsbmb.2015.06.014

    Article  CAS  Google Scholar 

  • Prough RA, Clark BJ, Klinge CM (2016) Novel mechanisms for DHEA action. J Mol Endocrinol 56:R139–R155. doi:10.1530/jme-16-0013

    Article  CAS  Google Scholar 

  • Psarra A-MG, Sekeris CE (2009) Glucocorticoid receptors and other nuclear transcription factors in mitochondria and possible functions. Biochimica et Biophysica Acta (BBA) - Bioenergetics 1787:431–436. doi:10.1016/j.bbabio.2008.11.011

    Article  CAS  Google Scholar 

  • Pugach EK, Blenck CL, Dragavon JM, Langer SJ, Leinwand LA (2016) Estrogen receptor profiling and activity in cardiac myocytes. Mol Cell Endocrinol 431:62–70. doi:10.1016/j.mce.2016.05.004

    Article  CAS  Google Scholar 

  • Pupo M et al (2012) Bisphenol A Induces Gene Expression Changes and Proliferative Effects through GPER in Breast Cancer Cells and Cancer-Associated Fibroblasts. Environ Health Perspect 120:1177–1182. doi:10.1289/ehp.1104526

    Article  CAS  Google Scholar 

  • Qiu J et al (2012) NYGGF4 (PID1) effects on insulin resistance are reversed by metformin in 3T3-L1 adipocytes. J Bioenerg Biomembr 44:665–671. doi:10.1007/s10863-012-9472-x

    Article  CAS  Google Scholar 

  • Radde BN, Ivanova MM, Mai HX, Salabei JK, Hill BG, Klinge CM (2015) Bioenergetic differences between MCF-7 and T47D breast cancer cells and their regulation by estradiol and tamoxifen. Biochem J 465:49–61. doi:10.1042/bj20131608

    Article  CAS  Google Scholar 

  • Radde BN et al (2016) Nuclear respiratory factor-1 and bioenergetics in tamoxifen-resistant breast cancer cells. Exp Cell Res. doi:10.1016/j.yexcr.2016.08.006

    Google Scholar 

  • Radi R, Peluffo G, Alvarez MN, Naviliat M, Cayota A (2001) Unraveling peroxynitrite formation in biological systems. Free Radic Biol Med 30:463–488. doi:10.1016/S0891-5849(00)00373-7

    Article  CAS  Google Scholar 

  • Radi R, Cassina A, Hodara R, Quijano C, Castro L (2002) Peroxynitrite reactions and formation in mitochondria. Free Radic Biol Med 33:1451–1464. doi:10.1016/S0891-5849(02)01111-5

    Article  CAS  Google Scholar 

  • Rasbach KA, Schnellmann RG (2008) Isoflavones Promote Mitochondrial Biogenesis. J Pharmacol Exp Ther 325:536–543. doi:10.1124/jpet.107.134882

    Article  CAS  Google Scholar 

  • Rettberg JR, Yao J, Brinton RD (2014) Estrogen: A master regulator of bioenergetic systems in the brain and body. Front Neuroendocrinol 35:8–30. doi:10.1016/j.yfrne.2013.08.001

    Article  CAS  Google Scholar 

  • Ribeiro MPC, Santos AE, Custódio JBA (2014) Mitochondria: The gateway for tamoxifen-induced liver injury. Toxicology 323:10–18. doi:10.1016/j.tox.2014.05.009

    Article  CAS  Google Scholar 

  • Ripperger T et al (2015) The heteromeric transcription factor GABP activates the ITGAM/CD11b promoter and induces myeloid differentiation Biochimica et. Biophysica Acta (BBA) - Gene Regulatory Mechanisms 1849:1145–1154. doi:10.1016/j.bbagrm.2015.07.005

    Article  CAS  Google Scholar 

  • Rodriguez-Cuenca S, Monjo M, Gianotti M, Proenza AM, Roca P (2007) Expression of mitochondrial biogenesis-signaling factors in brown adipocytes is influenced specifically by 17beta-estradiol, testosterone, and progesterone. Am J Physiol Endocrinol Metab 292:E340–E346. doi:10.1152/ajpendo.00175.2006

    Article  CAS  Google Scholar 

  • Rosmarin AG, Resendes KK, Yang Z, McMillan JN, Fleming SL (2004) GA-binding protein transcription factor: a review of GABP as an integrator of intracellular signaling and protein–protein interactions. Blood Cells Mol Dis 32:143–154. doi:10.1016/j.bcmd.2003.09.005

    Article  CAS  Google Scholar 

  • Safdar A, Little JP, Stokl AJ, Hettinga BP, Akhtar M, Tarnopolsky MA (2011) Exercise Increases Mitochondrial PGC-1α Content and Promotes Nuclear-Mitochondrial Cross-talk to Coordinate Mitochondrial Biogenesis. J Biol Chem 286:10605–10617. doi:10.1074/jbc.M110.211466

    Article  CAS  Google Scholar 

  • Sakurai M et al (2012) LIN28: A regulator of tumor-suppressing activity of let-7 microRNA in human breast cancer. J Steroid Biochem Mol Biol 131:101–106. doi:10.1016/j.jsbmb.2011.10.007

    Article  CAS  Google Scholar 

  • Salama SA et al (2014) Estradiol-17beta upregulates Pyruvate kinase M2 expression to co-activate estrogen receptor-alpha and to integrate metabolic reprogramming with the mitogenic response in endometrial cells. J Clin Endocrinol Metab jc20132639. doi:10.1210/jc.2013-2639

  • Sanchez MI, Shearwood AM, Chia T, Davies SM, Rackham O, Filipovska A (2015) Estrogen-mediated regulation of mitochondrial gene expression. Mol Endocrinol 29:14–27. doi:10.1210/me.2014-1077

    Article  CAS  Google Scholar 

  • Santolla MF et al (2015) SIRT1 is involved in oncogenic signaling mediated by GPER in breast cancer. Cell Death Dis 6:e1834. doi:10.1038/cddis.2015.201

    Article  CAS  Google Scholar 

  • Sarkar S, Jun S, Simpkins JW (2015) Estrogen amelioration of Aβ-induced defects in mitochondria is mediated by mitochondrial signaling pathway involving ERβ, AKAP and Drp1. Brain Res 1616:101–111. doi:10.1016/j.brainres.2015.04.059

    Article  CAS  Google Scholar 

  • Sastre-Serra J, Nadal-Serrano M, Pons DG, Roca P, Oliver J (2013) The over-expression of ERbeta modifies estradiol effects on mitochondrial dynamics in breast cancer cell line. Int J Biochem Cell Biol 45:1509–1515. doi:10.1016/j.biocel.2013.04.007

    Article  CAS  Google Scholar 

  • Satohisa S, Zhang HH, Feng L, Yang YY, Huang L, Chen DB (2014) Endogenous NO upon estradiol-17beta stimulation and NO donor differentially regulate mitochondrial S-nitrosylation in endothelial cells. Endocrinology 155:3005–3016. doi:10.1210/en.2013-2174

    Article  CAS  Google Scholar 

  • Scarpin KM, Graham JD, Mote PA, Clarke CL (2009) Progesterone action in human tissues: regulation by progesterone receptor (PR) isoform expression, nuclear positioning and coregulator expression. Nucl Recept Signal 7:e009. doi:10.1621/nrs.07009

    Google Scholar 

  • Scarpulla RC (2006) Nuclear control of respiratory gene expression in mammalian cells. J Cell Biochem 97:673–683

    Article  CAS  Google Scholar 

  • Scarpulla RC (2008) Transcriptional Paradigms in Mammalian Mitochondrial Biogenesis and Function. Physiol Rev 88:611–638. doi:10.1152/physrev.00025.2007

    Article  CAS  Google Scholar 

  • Scarpulla RC (2011) Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network Biochimica et. Biophysica Acta (BBA) - Molecular Cell Research 1813:1269–1278. doi:10.1016/j.bbamcr.2010.09.019

    Article  CAS  Google Scholar 

  • Scarpulla RC (2012) Nucleus-encoded regulators of mitochondrial function: Integration of respiratory chain expression, nutrient sensing and metabolic stress Biochimica et. Biophysica Acta (BBA) - Gene Regulatory Mechanisms 1819:1088–1097. doi:10.1016/j.bbagrm.2011.10.011

    Article  CAS  Google Scholar 

  • Scarpulla RC, Vega RB, Kelly DP (2012) Transcriptional integration of mitochondrial biogenesis. Trends in Endocrinology & Metabolism 23:459–466. doi:10.1016/j.tem.2012.06.006

    Article  CAS  Google Scholar 

  • Schmidt S, Strub A, Voos W (2001) Protein translocation into mitochondria. Biol Signals Recept 10:14–25

    Article  CAS  Google Scholar 

  • Schwend T, Gustafsson J-A (2006) False positives in MALDI-TOF detection of ER[beta] in mitochondria. Biochem Biophys Res Commun 343:707–711

    Article  CAS  Google Scholar 

  • Sepuri NBV, Tammineni P, Mohammed F, Paripati A (2016) Nuclear Transcription Factors in the Mitochondria: A New Paradigm in Fine-Tuning Mitochondrial Metabolism. In. Springer, Berlin Heidelberg, Berlin, pp 1–18. doi:10.1007/164_2016_3

    Google Scholar 

  • Sharma DR, Sunkaria A, Wani WY, Sharma RK, Kandimalla RJL, Bal A, Gill KD (2013) Aluminium induced oxidative stress results in decreased mitochondrial biogenesis via modulation of PGC-1α expression. Toxicol Appl Pharmacol 273:365–380. doi:10.1016/j.taap.2013.09.012

    Article  CAS  Google Scholar 

  • Silvente-Poirot S, Poirot M (2014) Cholesterol and Cancer, in the Balance. Science 343:1445–1446. doi:10.1126/science.1252787

    Article  Google Scholar 

  • Simoes DCM, Psarra A-MG, Mauad T, Pantou I, Roussos C, Sekeris CE, Gratziou C (2012) Glucocorticoid and Estrogen Receptors Are Reduced in Mitochondria of Lung Epithelial Cells in Asthma. PLoS One 7:e39183. doi:10.1371/journal.pone.0039183

    Article  CAS  Google Scholar 

  • Simpkins JW, Yang S-H, Sarkar SN, Pearce V (2008) Estrogen actions on mitochondria--Physiological and pathological implications. Mol Cell Endocrinol 290:51–59

    Article  CAS  Google Scholar 

  • Simpkins JW, Yi KD, Yang S-H, Dykens JA (2010) Mitochondrial mechanisms of estrogen neuroprotection Biochimica et. Biophysica Acta (BBA) - General Subjects 1800:1113–1120. doi:10.1016/j.bbagen.2009.11.013

    Article  CAS  Google Scholar 

  • Singh KP, Kumari R, Treas J, DuMond JW (2011) Chronic Exposure to Arsenic Causes Increased Cell Survival, DNA Damage, and Increased Expression of Mitochondrial Transcription Factor A (mtTFA) in Human Prostate Epithelial Cells. Chem Res Toxicol 24:340–349. doi:10.1021/tx1003112

    Article  CAS  Google Scholar 

  • Singhal H et al (2016) Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors in breast cancer. Sci Adv 2:e1501924. doi:10.1126/sciadv.1501924

    Article  Google Scholar 

  • Solakidi S, Psarra A-MG, Nikolaropoulos S, Sekeris CE (2005a) Estrogen receptors {alpha} and {beta} (ER{alpha} and ER{beta}) and androgen receptor (AR) in human sperm: localization of ER{beta} and AR in mitochondria of the midpiece. Hum Reprod 20:3481–3487

    Article  CAS  Google Scholar 

  • Solakidi S, Psarra AM, Sekeris CE (2005b) Differential subcellular distribution of estrogen receptor isoforms: Localization of ERalpha in the nucleoli and ERbeta in the mitochondria of human osteosarcoma SaOS-2 and hepatocarcinoma HepG2 cell lines. Biochim Biophys Acta 1745:382–392

    Article  CAS  Google Scholar 

  • Sotgia F et al (2012) Mitochondria "fuel" breast cancer metabolism: Fifteen markers of mitochondrial biogenesis label epithelial cancer cells, but are excluded from adjacent stromal cells. Cell Cycle 11:4390–4401. doi:10.4161/cc.22777

    Article  CAS  Google Scholar 

  • Spagnolo L, Barbeau J, Curtin NJ, Morris EP, Pearl LH (2012) Visualization of a DNA-PK/PARP1 complex. Nucleic Acids Res 40:4168–4177. doi:10.1093/nar/gkr1231

    Article  CAS  Google Scholar 

  • Stirone C, Duckles SP, Krause DN, Procaccio V (2005) Estrogen Increases Mitochondrial Efficiency and Reduces Oxidative Stress in Cerebral Blood Vessels. Mol Pharmacol 68:959–965

    Article  CAS  Google Scholar 

  • Sugden MC, Caton PW, Holness MJ (2010) PPAR control: it's SIRTainly as easy as PGC. J Endocrinol 204:93–104. doi:10.1677/joe-09-0359

    Article  CAS  Google Scholar 

  • Suliman HB, Sweeney TE, Withers CM, Piantadosi CA (2010) Co-regulation of nuclear respiratory factor-1 by NF{kappa}B and CREB links LPS-induced inflammation to mitochondrial biogenesis. J Cell Sci 123:2565–2575. doi:10.1242/jcs.064089

    Article  CAS  Google Scholar 

  • Suriyo T, Watcharasit P, Thiantanawat A, Satayavivad J (2012) Arsenite promotes apoptosis and dysfunction in microvascular endothelial cells via an alteration of intracellular calcium homeostasis. Toxicol in Vitro 26:386–395. doi:10.1016/j.tiv.2011.12.017

    Article  CAS  Google Scholar 

  • Tarnowski M et al (2010) Regulation of Expression of Stromal-Derived Factor-1 Receptors: CXCR4 and CXCR7 in Human Rhabdomyosarcomas. Mol Cancer Res 8:1–14. doi:10.1158/1541-7786.mcr-09-0259

    Article  CAS  Google Scholar 

  • Teng Y et al (2015) Dehydroepiandrosterone Activation of G-protein-coupled Estrogen Receptor Rapidly Stimulates MicroRNA-21 Transcription in Human Hepatocellular Carcinoma Cells. J Biol Chem 290:15799–15811. doi:10.1074/jbc.M115.641167

    Article  CAS  Google Scholar 

  • Theodorou V, Stark R, Menon S, Carroll JS (2013) GATA3 acts upstream of FOXA1 in mediating ESR1 binding by shaping enhancer accessibility. Genome Res 23:12–22. doi:10.1101/gr.139469.112

    Article  CAS  Google Scholar 

  • Thompson C, MacDonald G, Mueller C (2011) Decreased expression of BRCA1 in SK-BR-3 cells is the result of aberrant activation of the GABP Beta promoter by an NRF-1-containing complex. Mol Cancer 10:62

    Article  CAS  Google Scholar 

  • Totta P, Gionfra F, Busonero C, Acconcia F (2016) Modulation of 17beta-Estradiol Signaling on Cellular Proliferation by Caveolin-2. J Cell Physiol 231:1219–1225. doi:10.1002/jcp.25218

    Article  CAS  Google Scholar 

  • Umetani M (2016) Re-adopting classical nuclear receptors by cholesterol metabolites. J Steroid Biochem Mol Biol 157:20–26. doi:10.1016/j.jsbmb.2015.11.002

    Article  CAS  Google Scholar 

  • Umetani M, Shaul PW (2011) 27-Hydroxycholesterol: the first identified endogenous SERM. Trends in Endocrinology & Metabolism 22:130–135. doi:10.1016/j.tem.2011.01.003

    Article  CAS  Google Scholar 

  • Umetani M et al (2007) 27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen. Nat Med 13:1185–1192

    Article  CAS  Google Scholar 

  • van Heerde WL et al (2000) Markers of apoptosis in cardiovascular tissues: focus on Annexin V. Cardiovasc Res 45:549–559

    Article  Google Scholar 

  • Vaquerizas JM, Kummerfeld SK, Teichmann SA, Luscombe NM (2009) A census of human transcription factors: function, expression and evolution. Nat Rev Genet 10:252–263

    Article  CAS  Google Scholar 

  • Velickovic K et al (2014) Expression and subcellular localization of estrogen receptors alpha and beta in human fetal brown adipose tissue. J Clin Endocrinol Metab 99:151–159. doi:10.1210/jc.2013-2017

    Article  CAS  Google Scholar 

  • Vina J, Borras C, Gambini J, Sastre J, Pallardo FV (2005) Why females live longer than males? Importance of the upregulation of longevity-associated genes by oestrogenic compounds. FEBS Lett 579:2541–2545

    Article  CAS  Google Scholar 

  • Wadley GD, McConell GK (2010) High-dose antioxidant vitamin C supplementation does not prevent acute exercise-induced increases in markers of skeletal muscle mitochondrial biogenesis in rats. J Appl Physiol 108:1719–1726. doi:10.1152/japplphysiol.00127.2010

    Article  CAS  Google Scholar 

  • Wang Z-Y, Yin L (2015) Estrogen receptor alpha-36 (ER-α36): A new player in human breast cancer Mol Cell Endocrinol 418, Part 3:193–206 http://www.sciencedirect.com/science/article/pii/S0303720715002087

  • Wang C et al (2006) Cyclin D1 repression of nuclear respiratory factor 1 integrates nuclear DNA synthesis and mitochondrial function. PNAS 103:11567–11572. doi:10.1073/pnas.0603363103

    Article  CAS  Google Scholar 

  • Watson CS, Jeng Y-J, Guptarak J (2011) Endocrine disruption via estrogen receptors that participate in nongenomic signaling pathways. J Steroid Biochem Mol Biol 127:44–50. doi:10.1016/j.jsbmb.2011.01.015

    Article  CAS  Google Scholar 

  • Weitzel JM, Alexander Iwen K (2011) Coordination of mitochondrial biogenesis by thyroid hormone. Mol Cell Endocrinol 342:1–7. doi:10.1016/j.mce.2011.05.009

    Article  CAS  Google Scholar 

  • Whyte Warren A et al (2013) Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes. Cell 153:307–319. doi:10.1016/j.cell.2013.03.035

    Article  CAS  Google Scholar 

  • Wickramasekera NT, Das GM (2014) Tumor suppressor p53 and estrogen receptors in nuclear–mitochondrial communication. Mitochondrion 16:26–37. doi:10.1016/j.mito.2013.10.002

    Article  CAS  Google Scholar 

  • Wu Q et al (2013) 27-Hydroxycholesterol Promotes Cell-Autonomous, ER-Positive Breast Cancer Growth. Cell Rep 5:637–645. doi:10.1016/j.celrep.2013.10.006

  • Yang S-H et al (2004) Mitochondrial localization of estrogen receptor {beta}. PNAS 101:4130–4135

    Article  CAS  Google Scholar 

  • Yang S-H, Prokai L, Simpkins JW (2006) Correspondence regarding Schwend and Gustafsson, "False positives in MALDI-TOF detection of ER[beta] in mitochondria". Biochem Biophys Res Commun 345:917–918

    Article  CAS  Google Scholar 

  • Yao J, Brinton RD (2012) Estrogen Regulation of Mitochondrial Bioenergetics: Implications for Prevention of Alzheimer’s Disease. In: Elias KM, Mary LM (eds) Advances in Pharmacology, vol Volume 64. Academic Press, pp 327-371. Doi:10.1016/B978-0-12-394816-8.00010-6

  • Yao J, Chen S, Cadenas E, Brinton RD (2011) Estrogen protection against mitochondrial toxin-induced cell death in hippocampal neurons: Antagonism by progesterone. Brain Res 1379:2–10. doi:10.1016/j.brainres.2010.11.090

    Article  CAS  Google Scholar 

  • Yao J, Irwin R, Chen S, Hamilton R, Cadenas E, Brinton RD (2012) Ovarian hormone loss induces bioenergetic deficits and mitochondrial β-amyloid. Neurobiol Aging 33:1507–1521. doi:10.1016/j.neurobiolaging.2011.03.001

    Article  CAS  Google Scholar 

  • Zarrouk A et al (2015) Effects of cholesterol oxides on cell death induction and calcium increase in human neuronal cells (SK-N-BE) and evaluation of the protective effects of docosahexaenoic acid (DHA; C22:6 n-3). Steroids 99:Part B:238–Part B:247. doi:10.1016/j.steroids.2015.01.018

    Article  CAS  Google Scholar 

  • Zhai P, Eurell TE, Cooke PS, Lubahn DB, Gross DR (2000) Myocardial ischemia-reperfusion injury in estrogen receptor-alpha knockout and wild-type mice. Am J Physiol Heart Circ Physiol 278:H1640–H1647

    CAS  Google Scholar 

  • Zhang HH, Feng L, Wang W, Magness RR, Chen DB (2012) Estrogen-responsive nitroso-proteome in uterine artery endothelial cells: role of endothelial nitric oxide synthase and estrogen receptor-beta. J Cell Physiol 227:146–159. doi:10.1002/jcp.22712

    Article  CAS  Google Scholar 

  • Zhang M et al (2014) Lin28a Protects against Hypoxia/Reoxygenation Induced Cardiomyocytes Apoptosis by Alleviating Mitochondrial Dysfunction under High Glucose/High Fat Conditions. PLoS One 9:e110580. doi:10.1371/journal.pone.0110580

    Article  CAS  Google Scholar 

  • Zhang HH, Lechuga TJ, Tith T, Wang W, Wing DA, Chen DB (2015) S-nitrosylation of cofilin-1 mediates estradiol-17beta-stimulated endothelial cytoskeleton remodeling. Mol Endocrinol 29:434–444. doi:10.1210/me.2014-1297

    Article  CAS  Google Scholar 

  • Zhou Z, Zhou J, Du Y (2012) Estrogen receptor alpha interacts with mitochondrial protein HADHB and affects beta-oxidation activity. Mol Cell Proteomics 11(M111):011056. doi:10.1074/mcp.M111.011056

    Google Scholar 

  • Zou W et al (2015) Estrogen Receptor (ER)-α36 Is Involved in Estrogen- and Tamoxifen-Induced Neuroprotective Effects in Ischemic Stroke Models. PLoS One 10:e0140660. doi:10.1371/journal.pone.0140660

    Article  CAS  Google Scholar 

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Acknowledgements

Many thanks to Dr. Barbara J. Clark for her insightful editing of this review.

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  1. Department of Biochemistry & Molecular Genetics; Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY, 40292, USA

    Carolyn M. Klinge

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Klinge, C.M. Estrogens regulate life and death in mitochondria. J Bioenerg Biomembr 49, 307–324 (2017). https://doi.org/10.1007/s10863-017-9704-1

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