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Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
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Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
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Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
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Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
10:36

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Published on: March 17, 2016

Estrogen receptor beta as a mitochondrial vulnerability factor.

Shao-Hua Yang1, Saumyendra N Sarkar, Ran Liu

  • 1Department of Pharmacology and Neuroscience, Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, Texas 76107, USA. syang@hsc.unt.edu

The Journal of Biological Chemistry
|February 5, 2009
PubMed
Summary

Estrogen receptor beta (ERbeta) is found in mitochondria, acting as a vulnerability factor. Its knockdown increases resistance to oxidative stress and maintains mitochondrial membrane potential.

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Area of Science:

  • Mitochondrial biology
  • Neuroscience
  • Endocrinology

Background:

  • Estrogen receptor beta (ERbeta) has been recently shown to localize within mitochondria.
  • The precise role of mitochondrial ERbeta in cellular function and stress response remains largely unexplored.

Purpose of the Study:

  • To confirm the mitochondrial localization of ERbeta.
  • To investigate the functional consequences of mitochondrial ERbeta on cellular response to oxidative stress and mitochondrial homeostasis.

Main Methods:

  • Utilized ERbeta knockdown and knockout models in immortalized and primary hippocampal cells.
  • Assessed mitochondrial ERbeta immunoreactivity, mitochondrial membrane potential (Deltapsim), ATP concentrations, and mitochondrial superoxide production under oxidative stress conditions.

Main Results:

  • Confirmed mitochondrial localization of ERbeta through knockdown experiments, showing loss of immunoreactivity.
  • ERbeta knockdown led to increased resistance to oxidative stressors and hydrogen peroxide-induced Deltapsim depolarization.
  • ERbeta knockdown cells exhibited lower resting Deltapsim, maintained ATP levels during stress, and produced less mitochondrial superoxide.

Conclusions:

  • Estrogen receptor beta is functionally expressed in mitochondria.
  • Mitochondrial ERbeta acts as a vulnerability factor, influencing mitochondrial membrane potential maintenance and cellular response to oxidative stress.
  • These findings suggest a role for mitochondrial ERbeta in regulating mitochondrial transcription and overall cellular resilience.