120th General Meeting of the KCS

Type Symposium
Area Frontiers in Chemical Biology & Protein Chemistry
Room No. Room C311+C312
Time FRI 09:50-:
Code BIO-3
Subject Mitochondria Localization-induced Self-Assembly for New Cancer Therapy
Authors Ja-Hyoung Ryu
Department of Chemistry, Ulsan National Institute of Science and Technology, Korea
Abstract Self-assembled structures in Nature play essential roles in living systems, such as, in protein folding and the formation of biological membranes. The formation of most biological nanostructures is driven by self-assembly processes and the structured biomaterials have biochemical activities such as enzyme activity and protein signaling. The artificial assembly of synthetic building units inside a living cell and the interaction of these units with the cellular components have rarely been studied, but are emerging as an intriguing strategy to control cellular fate. In particular, self-assembly inside cellular organelles is challenging because of the practical difficulty in observing the complex intracellular environment, and thus has not yet been reported. Achievement of artificial self-assembly of small molecules inside such organelles could be an advanced strategy for an efficient external control over organelle function and manipulation of the cellular fate. Considering the role of vicious mitochondrial fibril proteins such as amyloid beta (Aβ) in Alzheimer’s disease, we hypothesized that artificial induction of fibril formation inside the mitochondria could promote mitochondrial dysfunction and induce cell damage. Amphiphilic peptides with a mitochondrial targeting unit selectively accumulate in the mitochondria and self-assemble into an ordered structure because inside the confined organelle, the concentration of the peptides is significantly increased over their critical aggregation concentration. The fibrous structure inside the mitochondria then disrupts the mitochondrial membrane to cause leakage of the mitochondrial contents into the cytosol, resulting in severe damage to the cells. The high negative membrane potential of mitochondria in cancer cells increased the accumulation of Mito-FF, which resulted in selective supramolecular assembly in the cancer cells.
E-mail jhryu@unist.ac.kr