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Chem Biol. 2008 Apr;15(4):375-82. doi: 10.1016/j.chembiol.2008.03.015.

Mitochondria-penetrating peptides.

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Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, ON M5S 3M2, Canada.


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.

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