Development of lipophilic cations as therapies for disorders due to mitochondrial dysfunction

Expert Opin Biol Ther. 2001 Sep;1(5):753-64. doi: 10.1517/14712598.1.5.753.


Mitochondrial dysfunction causes or exacerbates a number of diseases. These include genetic disorders such as Friedreich's ataxia where the primary lesion is a defect in a nuclear gene and those diseases caused by mutations to mitochondrial DNA. Mitochondrial damage also contributes to neurodegenerative diseases, diabetes and ischaemia-reperfusion injury. Drug therapies to prevent or alleviate mitochondrial dysfunction use redox active compounds, anti-oxidants or mitochondrial co-factors, however, their effectiveness is limited. A promising approach to increase the selectivity and potency of these compounds is to modify them so that they concentrate within mitochondria. This can be done by incorporating a lipophilic cation which causes the molecules to concentrate several hundred-fold in mitochondria, driven by the membrane potential across the inner membrane. As lipophilic cations cross biological membranes easily, they can be delivered to mitochondria of the heart, brain and skeletal muscle, the organs most affected by mitochondrial damage. Mitochondria-targeted lipophilic cations may lead to improved therapies for diseases involving mitochondrial dysfunction.

Publication types

  • Review

MeSH terms

  • Animals
  • Cations / chemical synthesis*
  • Cations / therapeutic use*
  • Humans
  • Lipid Metabolism*
  • Mitochondrial Diseases / drug therapy*
  • Mitochondrial Diseases / metabolism
  • Onium Compounds / chemical synthesis
  • Onium Compounds / therapeutic use
  • Organ Specificity
  • Technology, Pharmaceutical / methods*
  • Trityl Compounds / chemical synthesis
  • Trityl Compounds / therapeutic use


  • Cations
  • Onium Compounds
  • Trityl Compounds
  • triphenylmethylphosphonium