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

Jin Qiang Chen, Patrick R. Cammarata, Christopher P. Baines, James D. Yager

Research output: Contribution to journalReview articlepeer-review

Abstract

There has been increasing evidence pointing to the mitochondrial respiratory chain (MRC) as a novel and important target for the actions of 17β-estradiol (E2) and estrogen receptors (ER) in a number of cell types and tissues that have high demands for mitochondrial energy metabolism. This novel E2-mediated mitochondrial pathway involves the cooperation of both nuclear and mitochondrial ERα and ERβ 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 E2/ER-mediated MRC biogenesis pathway.

Original languageEnglish (US)
Pages (from-to)1540-1570
Number of pages31
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1793
Issue number10
DOIs
StatePublished - Oct 2009

Keywords

  • Alzheimer's disease
  • Anti-cancer drug resistance
  • Cataract
  • Estrogen
  • Estrogen carcinogenesis in breast cancer
  • Estrogen protection of cardiovascular disease
  • Estrogen receptor
  • Mitochondrial DNA replication
  • Mitochondrial estrogen receptor
  • Mitochondrial transcription factor A
  • Nuclear respiratory factor
  • Parkinson's disease
  • Respiratory chain biogenesis
  • Transcription and translation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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