Mitochondrial estrogen receptors--new insights into specific functions.

Estrogen receptor (ER) alpha and ERbeta are present in mitochondria but little is known about their contribution to the overall constellation of cellular responses to 17beta-estradiol, which inhibits the early stages of apoptosis through membrane and mitochondrial, but not nuclear, ER signaling pathways. Whereas membrane ER signaling leading to inhibition of apoptosis involves the activation of protein kinase pathways, mitochondrial ER-mediated inhibition involves the direct and/or indirect activation of manganese superoxide dismutase by the mitochondrial ER.

Binding of MCF-7 cell mitochondrial proteins and recombinant human estrogen receptors alpha and beta to human mitochondrial DNA estrogen response elements.

Our previous studies have shown that 17beta estradiol (E2) enhances the transcript levels of mitochondrial DNA (mtDNA)-encoded genes and mitochondrial respiratory chain (MRC) activity via estrogen receptors (ER). Others have reported the presence of putative estrogen responsive elements (ERE) in human mtDNA (mtEREs) and detection of ERs in mitochondria of rat uterine and ovary cells. Recently, we demonstrated the E2-enhanced mitochondrial localization of ERalpha and ERbeta, and E2-induced mtDNA transcript levels in MCF-7 cells.

Mitochondrial localization of ERalpha and ERbeta in human MCF7 cells.

We observed previously that estrogen treatment increased the transcript levels of several mitochondrial DNA (mtDNA)-encoded genes for mitochondrial respiratory chain (MRC) proteins and MRC activity in rat hepatocytes and human Hep G2 cells. Others have reported detection of estrogen receptors (ER), ERalpha and ERbeta, in mitochondria of rabbit ovarian and uterine tissue. In this study, we have extended these observations.