Mitochondrial uncoupling as a therapeutic target following neuronal injury

J Bioenerg Biomembr. 2004 Aug;36(4):353-6. doi: 10.1023/B:JOBB.0000041767.30992.19.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Brain Injuries / complications
  • Brain Injuries / drug therapy*
  • Brain Injuries / metabolism*
  • Calcium / metabolism
  • Carrier Proteins / metabolism*
  • Drug Delivery Systems / methods
  • Humans
  • Ion Channels
  • Membrane Proteins / metabolism*
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Mitochondrial Diseases / drug therapy
  • Mitochondrial Diseases / etiology
  • Mitochondrial Diseases / metabolism
  • Mitochondrial Proteins
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurons / pathology
  • Neuroprotective Agents / administration & dosage*
  • Reactive Oxygen Species / metabolism
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / metabolism*
  • Uncoupling Protein 1


  • Carrier Proteins
  • Ion Channels
  • Membrane Proteins
  • Mitochondrial Proteins
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Uncoupling Protein 1
  • Calcium