Mitochondrial uncoupling as a therapeutic target following neuronal injury

P. G. Sullivan, Joe E. Springer, Edward D. Hall, Stephen W. Scheff

Research output: Contribution to journalArticlepeer-review

108 Scopus citations


Mitochondrial dysfunction is a prominent feature of excitotoxic insult and mitochondria are known to play a pivotal role in neuronal cell survival and death following injury. Following neuronal injury there is a well-documented increase in cytosolic Ca 2+, reactive oxygen species (ROS) production and oxidative damage. In vitro studies have demonstrated these events are dependent on mitochondrial Ca 2+ cycling and that a reduction in membrane potential is sufficient to reduce excitotoxic cell death. This concept has gained additional support from experiments demonstrating that the overexpression of endogenous mitochondrial uncoupling proteins (UCP), which decrease the mitochondrial membrane potential, decreases cell death following oxidative stress. Our group has demonstrated that upregulation of UCP activity can reduce excitotoxic-mediated ROS production and cell death whereas a reduction in UCP levels increases susceptibility to neuronal injury. These findings raise the possibility that mitochondrial uncoupling could be a potential novel treatment for acute CNS injuries.

Original languageEnglish
Pages (from-to)353-356
Number of pages4
JournalJournal of Bioenergetics and Biomembranes
Issue number4 SPEC.ISS.
StatePublished - Aug 2004


  • excitotoxicity
  • Neuronal cell death
  • reactive oxygen species
  • spinal cord injury
  • traumatic brain injury

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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