Organelle-specific subcellular delivery using mitochondria-penetrating peptides.
The mitochondrion is the powerhouse of the cell and also plays a key role in regulating programmed cell death. In particular, the elucidation of the mitochondrion’s function in various human diseases has generated an appreciable amount of interest in exploring this organelle as a potential drug target. Delivering molecular agents to mitochondria is challenging, however, due to the difficulty of penetrating the hydrophobic inner mitochondrial membrane. We have developed a set of peptide-based agents that are able to carry drug molecules into mitochondria, and have studied the effects of delivering clinically used anticancer and antibacterial agents to mitochondrial targets. We have also mitochodnrially-targeted drug conjugates to discover new proteins with previously undetected activities in this cellular subcompartment. Our work on using this approach to i) perform high-througput screens for mitochondrial proteins, ii) develop new approaches to combat drug resistance and iii) define structure-function relationships controlling mitochondrial transport will be presented.