Molecular targets of estrogen in regulating mitochondrial function. 1. Estrogen binds to nuclear estrogen receptors (ERα and ERβ) to directly regulate tissue-specific expression of genes necessary for cellular function. 2. Estrogen binds to nuclear ERs and regulates expression of mitochondrial genes by promoting gene expression of transcription factor NRF1 and enhancing transcriptional activity of PGC1α. 3. Estrogen binds to membrane ERs and activates signaling cascades that protect mitochondria from oxidative damage. 4. Estrogen binds to mitochondrial ERs and limits ROS generation in the mitochondria. 5. Estrogen binds to mitochondrial ERs and regulates transcription of mitochondrial-encoded mitochondrial genes.