A function for novel uncoupling proteins: antioxidant defense of mitochondrial matrix by translocating fatty acid peroxides from the inner to the outer membrane leaflet

FASEB J. 2003 Sep;17(12):1585-91. doi: 10.1096/fj.03-0159hyp.


It is hypothesized that mitochondrial uncoupling proteins operate as carriers of fatty acid peroxide anions. This is assumed to result in electrophoretic extrusion of such anions from the inner to the outer leaflet of the inner mitochondrial membrane, being driven by membrane potential (mitochondrial interior negative). In this way, the inner leaflet is ridded of fatty acid peroxides that otherwise can form very aggressive oxidants damaging mitochondrial DNA, aconitase, and other mitochondrial matrix-localized components of vital importance. The steady-state concentration the fatty acid peroxides is known to be low. This explains why UCP2, 3, 4, and 5 are present in small amounts usually insufficient to make a large contribution to the H+ conductance of the mitochondrial membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / metabolism
  • Carrier Proteins / physiology*
  • Intracellular Membranes / metabolism*
  • Lipid Peroxides / metabolism*
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / physiology*
  • Models, Biological
  • Protein Transport


  • Antioxidants
  • Carrier Proteins
  • Lipid Peroxides
  • Mitochondrial Proteins