Estrogen Receptor β as a Mitochondrial Vulnerability Factor

We recently demonstrated mitochondrial localization of estrogen receptor beta ( ER beta). We herein confirm the mitochondrial localization of ER beta by the loss of mitochondrial ER beta immunoreactivity in ER beta knockdown cells. Aphenotype change characterized as an increase in resistance to oxidative stressors is associated with ER beta knockdown. ER beta knockdown results in a lower resting mitochondrial membrane potential (Delta psi m) and increase in resistance to hydrogen peroxide-induced Delta psi m depolarization in both immortal hippocampal cells and primary hippocampal neurons. ER beta 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 ER beta knock-out mice. These data demonstrate that ER beta is expressed in mitochondria and function as a mitochondrial vulnerability factor involved in Delta psi m maintenance, potentially through a mitochondrial transcription dependent mechanism.