Antipodean Pharmaceuticals, Inc. is developing a mitochondria-targeted antioxidant, MitoQ^® (mitoquinone mesylate), for treatment of hepatic inflammatory disorders caused by oxidative stress, such as nonalcoholic steatohepatitis (NASH).

Mitochondria-targeted antioxidants are produced by covalently bonding antioxidant moieties to a triphenylphosphonium (TPP) cation.  These antioxidants can rapidly permeate lipid bilayers after oral administration and may accumulate within the mitochondria in organs most affected by mitochondrial dysfunction, such as the brain, heart, skeletal muscle, and liver. Mitoquinone is a targeted version of ubiquinone, a lipid-soluble coenzyme found in the mitochondria of all living cells.  For mitoquinone, a ubiquinone head group is attached to a triphenylphosphonium lipophilic cation via a 10-carbon aliphatic chain.

The MitoQ^® structure was designed to deliver and position the active ubiquinone moiety to the phospholipid bilayer in the inner membrane of mitochondria.  MitoQ^® is adsorbed on the inner, matrix-facing surface of the mitochondrial inner membrane with the phosphonium cation adsorbed to the surface of the membrane while the hydrophobic ubiquinone moiety is inserted into the membrane.  Localization to the inner surface of the mitochondrial membrane positions mitoquinone to the region where most ROS originate and where most of the critical components of mitochondrial oxidative phosphorylation are located. 

In an in vitro model of mitochondrial dysfunction, mitoquinone was shown to be 1000 times more potent than the untargeted ubiquinones in protecting mitochondria from lipid peroxidation and triggering cell apoptosis.  .