Regulation of mitochondrial respiratory chain biogenesis by estrogens/estrogen receptors and physiological, pathological and pharmacological implications

Biochim Biophys Acta. 2009 Oct;1793(10):1540-70. doi: 10.1016/j.bbamcr.2009.06.001. Epub 2009 Jun 23.


There has been increasing evidence pointing to the mitochondrial respiratory chain (MRC) as a novel and important target for the actions of 17beta-estradiol (E(2)) and estrogen receptors (ER) in a number of cell types and tissues that have high demands for mitochondrial energy metabolism. This novel E(2)-mediated mitochondrial pathway involves the cooperation of both nuclear and mitochondrial ERalpha and ERbeta and their co-activators on the coordinate regulation of both nuclear DNA- and mitochondrial DNA-encoded genes for MRC proteins. In this paper, we have: 1) comprehensively reviewed studies that reveal a novel role of estrogens and ERs in the regulation of MRC biogenesis; 2) discussed their physiological, pathological and pharmacological implications in the control of cell proliferation and apoptosis in relation to estrogen-mediated carcinogenesis, anti-cancer drug resistance in human breast cancer cells, neuroprotection for Alzheimer's disease and Parkinson's disease in brain, cardiovascular protection in human heart and their beneficial effects in lens physiology related to cataract in the eye; and 3) pointed out new research directions to address the key questions in this important and newly emerging area. We also suggest a novel conceptual approach that will contribute to innovative regimens for the prevention or treatment of a wide variety of medical complications based on E(2)/ER-mediated MRC biogenesis pathway.

Publication types

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

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / etiology
  • Animals
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / etiology
  • Cardiovascular Diseases / prevention & control
  • Cell Proliferation
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism
  • Drug Resistance, Neoplasm
  • Electron Transport / drug effects*
  • Electron Transport / genetics
  • Electron Transport / physiology*
  • Estradiol / pharmacology
  • Estradiol / physiology
  • Estrogens / physiology*
  • Female
  • Genome, Mitochondrial
  • Humans
  • Lens, Crystalline / drug effects
  • Lens, Crystalline / physiology
  • Male
  • Mitochondria / drug effects*
  • Mitochondria / genetics
  • Mitochondria / physiology*
  • Mitochondrial Proteins / physiology
  • Mitochondrial Proton-Translocating ATPases / physiology
  • Models, Biological
  • Neoplasms, Hormone-Dependent / drug therapy
  • Neoplasms, Hormone-Dependent / etiology
  • Neuroprotective Agents / pharmacology
  • Parkinson Disease / drug therapy
  • Parkinson Disease / etiology
  • Protein Biosynthesis / drug effects
  • Receptors, Estrogen / physiology*
  • Transcription, Genetic / drug effects


  • DNA, Mitochondrial
  • Estrogens
  • Mitochondrial Proteins
  • Neuroprotective Agents
  • Receptors, Estrogen
  • Estradiol
  • Mitochondrial Proton-Translocating ATPases