“…So far two major apoptotic pathways have been characterized: the death receptor-mediated, or extrinsic pathway, and the mitochondria-mediated apoptosis or intrinsic pathway. The role played by mitochondria in apoptosis makes these cellular organelles desired targets for therapeutic drugs. − Currently, several strategies for the delivery of biologically active molecules to the mitochondria of live mammalian cells are widely used: (1) tethering a mitochondrial localization peptide sequence, which utilizes protein import pathway; (2) attaching a lipophilic cation group, which utilizes the high membrane potential (180 mV) across the inner mitochondrial membrane; and (3) using lyposome-based carrier (e.g., vesicle) for transporting large or vulnerable cargo. , As for the lipophilic cation approach, Murphy, Chang, and so on have designed a series of triphenylphosphonium-based bioactive molecules with excellent mitochondria targeting capability. ,, The delocalized positive charge in these lipophilic cations enables them to permeate lipid bilayers easily and to accumulate several hundred-fold within mitochondria because of the large mitochondrial membrane potential (∼180 mV, negative inside). In addition to triphenylphosphonium, some other lipophilic cations, like ammonium-containing cations were also found to be able to target mitochondria.…”