Mitochondrial targeting of quinones: therapeutic implications.
Mitochondrial oxidative damage contributes to a range of degenerative diseases. Ubiquinones have been shown to protect mitochondria from oxidative damage, but only a small proportion of externally administered ubiquinone is taken up by mitochondria. Conjugation of the lipophilic triphenylphosphonium cation to a ubiquinone moiety has produced a compound, MitoQ, which accumulates selectively into mitochondria. MitoQ passes easily through all biological membranes and, because of its positive charge, is accumulated several hundred-fold within mitochondria driven by the mitochondrial membrane potential. MitoQ protects mitochondria against oxidative damage in vitro and following oral delivery, and may therefore form the basis for mitochondria-protective therapies.
Cochemé
Helena M
HM
MRC Dunn Human Nutrition Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, UK.
Kelso
Geoffrey F
GF
James
Andrew M
AM
Ross
Meredith F
MF
Trnka
Jan
J
Mahendiran
Thabo
T
Asin-Cayuela
Jordi
J
Blaikie
Frances H
FH
Manas
Abdul-Rahman B
AR
Porteous
Carolyn M
CM
Adlam
Victoria J
VJ
Smith
Robin A J
RA
Murphy
Michael P
MP
D000284:Administration, Oral; D000818:Animals; D002412:Cations; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000628:therapy; D008954:Models, Biological; D008956:Models, Chemical; D009943:Organophosphorus Compounds / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D011809:Quinones / Q000737:chemistry*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism
D002412:Cations; D009943:Organophosphorus Compounds; D011809:Quinones; D014451:Ubiquinone; C429014:mitoquinone; D010100:Oxygen