FIG. 9.

Targeting compounds to mitochondria by conjugation to the lipophilic cation TPP. TPP has a large, hydrophobic surface area that enables it to pass easily through phospholipid bilayers. The molecule first passes through the plasma membrane and accumulates in the cytosol driven by the plasma membrane potential (Δψ_p). This strategy further utilizes the large Δψ_m (negative inside) to drive accumulation of TPP⁺-linked bioactive compounds inside mitochondria for several hundred fold. The antioxidant properties of the conjugates are exploited inside the mitochondrial compartment, and the oxidized forms are then re-reduced (recycled) by ETC complexes.