Mitochondrial localization of estrogen receptor

Estrogen receptors (ERs) are believed to be ligand-activated transcription factors belonging to the nuclear receptor superfamily, which on ligand binding translocate into the nucleus and activate gene transcription. To date, two ERs have been identified: ER and ER . ER plays major role in the estrogen-mediated genomic actions in both reproductive and nonreproductive tissue, whereas the function of ER is still unclear. In this study, we used immunocytochemistry, immunoblotting, and proteomics to demonstrate that ER localizes to the mitochondria. In immunocytochemistry studies, ER was detected with two ER antibodies and found to colocalize almost exclusively with a mitochondrial marker in rat primary neuron, primary cardiomyocyte, and a murine hippocampal cell line. The colocalization of ER and mitochondrial markers was identified by both fluorescence and confocal microscopy. No translocation of ER into the nucleus on 17 -estradiol treatment was seen by using immunocytochemistry. Immunoblotting of purified human heart mitochondria showed an intense signal of ER , whereas no signals for nuclear and other organelle markers were found. Finally, purified human heart mitochondrial proteins were separated by SDS PAGE. The 50,000–65,000 Mr band was digested with trypsin and subjected to matrix-assisted laser desorption ionization mass spectrometric analysis, which revealed seven tryptic fragments that matched with those of ER . In summary, this study demonstrated that ER is localized to mitochondria, suggesting a role for mitochondrial ER in estrogen effects on this important organelle.