Mitochondrial translocation of estrogen receptor β affords resistance to oxidative insult-induced apoptosis and contributes to the pathogenesis of endometriosis

Tien Ling Liao, Yu Ching Lee, Chii Ruey Tzeng, Yi Pei Wang, Heng Yu Chang, Yung Feng Lin, Shu Huei Kao

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Endometriosis is the major cause of female infertility and has been linked to the action of estrogen and estrogen receptor (ER). A new pool of ERβ locates within mitochondria, which regulates the endometriotic cell withstanding external insults, but its effect remains controversial. We hypothesize that mitochondrial estrogen receptor ERβ (mtERβ) is a pivotal regulator in estradiol-mediated cell protection leading to the endometriotic progression. We observed elevated levels of ERβ in the endometriotic tissues. A dramatic increase of ERβ in mitochondria (mtERβ) was found in the ectopic endometriotic tissues, or the estradiol-primed primary endometriotic cells. We analyzed the mtERβ-specific overexpressing clone (mtsERβ), which exhibited higher mitochondrial bioenergetics and lower reactive oxygen species (ROS) generation. The mtsERβ-overexpressed endometriotic cells displayed an enhanced migration phenotype, whereas significantly attenuated migration by mitochondrial respiratory inhibitor (oligomycin) or ERβ deficiency by shERβ. Further investigations revealed that ERβ directly modulated mitochondrial DNA (mtDNA) gene expression by interacting with mtDNA D-loop and polymerase γ. The mtsERβ afforded a resistance to oxidative insult-induced apoptosis through the induction of the ROS scavenger enzyme Mn-superoxide dismutase and anti-apoptotic protein Bcl-2. Collectively, the demonstration of mtERβ responses in restoration of mitochondrial bioenergetics and inhibition of mitochondria-dependent apoptotic events provides insight into the pathogenesis of endometriosis, suggesting ERβ-selective estrogen receptor modulator may serve as novel therapeutics of endometriosis in the future.

Original languageEnglish
Pages (from-to)359-373
Number of pages15
JournalFree Radical Biology and Medicine
Volume134
DOIs
Publication statusPublished - Apr 1 2019

Keywords

  • Anti-apoptosis
  • Cell migration
  • Endometriosis
  • Mitochondrial bioenergetics
  • Mitochondrial estrogen receptor β
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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