Estrogenic control of mitochondrial function and biogenesis

J Cell Biochem. 2008 Dec 15;105(6):1342-51. doi: 10.1002/jcb.21936.


Estrogens have cell-specific effects on a variety of physiological endpoints including regulation of mitochondrial biogenesis and activity. Estrogens regulate gene transcription by the classical genomic mechanism of binding to estrogen receptors alpha and beta (ERalpha and ERbeta) as well as the more recently described nongenomic pathways involving plasma membrane-associated ERs that activate intracellular protein kinase-mediated phosphorylation signaling cascades. Here I will review the rapid and longer-term effects of estrogen on mitochondrial function. The identification of ERalpha and ERbeta within mitochondria of various cells and tissues is discussed with a model of estrogen regulation of the transcription of nuclear respiratory factor-1 (NRF-1, NRF1). NRF-1 subsequently promotes transcription of mitochondrial transcription factor Tfam (mtDNA maintenance factor, also called mtTFA) and then Tfam targets mtDNA-encoded genes. The nuclear effects of estrogens on gene expression directly controlling mitochondrial biogenesis, oxygen consumption, mtDNA transcription, and apoptosis are reviewed. Overall, we are just beginning to evaluate the many direct and indirect effects of estrogens on mitochondrial activities.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Apoptosis
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / metabolism
  • Estrogens / metabolism*
  • Genome
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Models, Biological
  • NF-E2-Related Factor 1 / genetics
  • NF-E2-Related Factor 1 / metabolism
  • Oxygen / metabolism
  • Raloxifene Hydrochloride / metabolism
  • Raloxifene Hydrochloride / pharmacology
  • Transcription, Genetic


  • DNA, Mitochondrial
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Estrogens
  • NF-E2-Related Factor 1
  • Raloxifene Hydrochloride
  • Oxygen