Mitochondria-penetrating peptides

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

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane / metabolism
  • HeLa Cells
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Mitochondria / metabolism*
  • Peptides / chemistry*
  • Peptides / metabolism*
  • Permeability
  • Protein Engineering / methods*
  • Protein Transport
  • Sensitivity and Specificity

Substances

  • Peptides