Figure 5.

Schematic representation of targeting mitochondria by different molecules. A generic mitochondria-targeted antioxidant is shown constructed by the covalent attachment of an antioxidant molecule to the lipophilic triphenylphosphonium cation. Antioxidant molecules accumulate 5-10 fold in the cytoplasm, which is driven by plasma membrane potential, and then further accumulates 100-500 fold in the mitochondria. Mitochondria-targeted molecules rapidly neutralize free radicals and reduce mitochondrial toxicity. The SS31 is a cell-permeable tetra-peptide that targeted to mitochondria and protects mitochondria from oxidative damage. SS31 peptide has a sequence motif that allows them to target mitochondria several hundred fold more than natural antioxidants. Once SS peptides reach mitochondria, the SS peptides rapidly neutralize free radicals and decrease mitochondrial toxicity.