title: Mitochondrial estrogen receptor β inhibits cell apoptosis via interaction with Bad in a ligand-independent manner.
abstract: Previous studies reported that estrogen receptor β (ERβ) is localized to mitochondria, whereas little is known about the physiological functions of mitochondrial ERβ. In the present study, we explored the role of mitochondrial ERβ in regulating apoptosis using stable ERβ-expressing and ERβ knockdown cells lines. We found that exogenous ERβ was mainly expressed in mitochondrial but not in nuclear after ERβ overexpression and protected cells from apoptosis induced by hydrogen peroxide (H₂O₂), ultraviolet (UV), and staurosporine (STS). Moreover, overexpression of ERβ prevented Bax activation, cytochrome c release, caspase-3 activation, and PARP cleavage during apoptosis. Furthermore, knockdown of ERβ significantly suppressed the expression of ERβ in mitochondrial and promoted cell apoptosis induced by H₂O₂, UV, and STS. Downregulation of ERβ also enhanced Bax activation, cytochrome c release, caspase-3 activation and PARP cleavage. In addition, our study discovered that mitochondrial ERβ interacted with proapoptotic protein Bad in a ligand-independent manner, which suggests that mitochondrial ERβ inhibits Bad, and prevents Bax activation and cytochrome c release. Collectively, the results of this study support that mitochondrial ERβ prevents cell apoptosis via the mitochondrial apoptotic pathway in a ligand-independent manner.
authors.affiliation: Department of Hematology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Liang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xie
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Xueyun
authors.initials: X
authors.lastname: Zhong
authors.forename: Yunxian
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D019556:COS Cells; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D061986:MCF-7 Cells; D008928:Mitochondria / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D051025:bcl-Associated Death Protein / Q000378:metabolism*
chemical_list: C494819:BAD protein, human; C000600034:ESR2 protein, human; D047629:Estrogen Receptor beta; D051025:bcl-Associated Death Protein; D006861:Hydrogen Peroxide; D019311:Staurosporine