Mitochondria-penetrating peptides.
Mitochondria are important targets for cancer chemotherapy and other disease treatments. Gaining access to this organelle can be difficult, as the inner membrane is a barrier limiting diffusive transport. A mitochondrial molecular carrier would be a boon to the development of organelle-specific therapeutics. Here, we report a significant advance in the development of mitochondrial transporters-synthetic cell-permeable peptides that are able to enter mitochondria. Efficient uptake of these mitochondria-penetrating peptides (MPPs) is observed in a variety of cell types, and organellar specificity is attained with sequences that possess specific chemical properties. The MPPs identified are cationic, but also lipophilic; this combination of characteristics facilitates permeation of the hydrophobic mitochondrial membrane. The examination of a panel of MPPs illustrates that mitochondrial localization can be rationally controlled and finely tuned by altering lipophilicity and charge.
Horton
Kristin L
KL
Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, ON M5S 3M2, Canada.
Stewart
Kelly M
KM
Fonseca
Sonali B
SB
Guo
Qian
Q
Kelley
Shana O
SO
D002462:Cell Membrane / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008928:Mitochondria / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D010539:Permeability; D015202:Protein Engineering / Q000379:methods*; D021381:Protein Transport; D012680:Sensitivity and Specificity
D010455:Peptides