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Estrogenic control of mitochondrial function.

Carolyn M Klinge1

  • 1Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, 40292, KY, USA.

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Estrogens regulate mitochondrial metabolism and function through nuclear and mitochondrial pathways. This review details how estrogens impact cellular functions, gene transcription, and mitochondrial dynamics.

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EstrogenEstrogen receptorGPER1MitochondriaNRF-1Sex-differences

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Area of Science:

  • Endocrinology and Metabolism
  • Mitochondrial Biology
  • Molecular Endocrinology

Background:

  • Sex-based differences in disease are influenced by sex steroid hormones regulating mitochondrial metabolism.
  • Estrogens, produced by various tissues, play a crucial role in cellular functions.
  • Estrogen receptors (ERα, ERβ, GPER1) mediate estrogen's effects on cellular processes.

Purpose of the Study:

  • To provide an updated review on how estrogens regulate metabolism and mitochondrial function.
  • To elucidate the mechanisms by which estrogens influence cellular functions and mitochondrial dynamics.
  • To highlight the role of nuclear respiratory factor-1 (NRF-1) in estrogen-mediated mitochondrial regulation.

Main Methods:

  • Review of existing literature on estrogen's effects on mitochondrial metabolism.
  • Analysis of cellular and molecular mechanisms involving estrogen receptors.
  • Examination of transcriptional regulation of nuclear and mitochondrial genes.

Main Results:

  • Estrogens regulate mitochondrial metabolism and morphology via nuclear and mitochondrial pathways.
  • Estrogen receptors (ERα, ERβ) act as transcription factors, influencing gene expression.
  • Estrogen signaling stimulates nuclear respiratory factor-1 (NRF-1) and coactivators like PGC-1α, regulating mitochondrial gene expression.
  • Estrogen impacts mitochondrial bioenergetics, oxygen consumption rate (OCR), and extracellular acidification (ECAR).

Conclusions:

  • Estrogens are key regulators of mitochondrial metabolism and function through diverse cellular mechanisms.
  • Estradiol's actions involve both genomic and non-genomic signaling pathways.
  • Understanding these mechanisms is crucial for addressing sex-based differences in disease and developing targeted therapies.