title: Estrogen receptor beta as a mitochondrial vulnerability factor.
abstract: We recently demonstrated mitochondrial localization of estrogen receptor beta (ERbeta). We herein confirm the mitochondrial localization of ERbeta by the loss of mitochondrial ERbeta immunoreactivity in ERbeta knockdown cells. A phenotype change characterized as an increase in resistance to oxidative stressors is associated with ERbeta knockdown. ERbeta knockdown results in a lower resting mitochondrial membrane potential (Deltapsim) and increase in resistance to hydrogen peroxide-induced Deltapsim depolarization in both immortal hippocampal cells and primary hippocampal neurons. ERbeta knockdown cells maintained ATP concentrations despite insults that compromise ATP production and produce less mitochondrial superoxide under oxidative stress. Furthermore, similar mitochondrial phenotype changes were identified in primary hippocampal neurons derived from ERbeta knock-out mice. These data demonstrate that ERbeta is expressed in mitochondria and function as a mitochondrial vulnerability factor involved in Deltapsim maintenance, potentially through a mitochondrial transcription dependent mechanism.
authors.affiliation: Department of Pharmacology and Neuroscience, Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, Texas 76107, USA. syang@hsc.unt.edu
authors.forename: Shao-Hua
authors.initials: SH
authors.lastname: Yang
authors.forename: Saumyendra N
authors.initials: SN
authors.lastname: Sarkar
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.forename: Evelyn J
authors.initials: EJ
authors.lastname: Perez
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Wen
authors.forename: Liang-Jun
authors.initials: LJ
authors.lastname: Yan
authors.forename: James W
authors.initials: JW
authors.lastname: Simpkins
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D047629:Estrogen Receptor beta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D046509:Tissue Culture Techniques
chemical_list: D047629:Estrogen Receptor beta