Intramitochondrial polymerization induced self-assembly for regulating cellular fate

Abstract

The intracellular biomacromolecules including proteins, DNA, and polysaccharides, play an important role to perform cellular function. Theses macromolecules are synthesized by self-assembly of building blocks such as amino acids, nucleotides, and monossacharides, which leads to construct complex and high ordered structure. The functionality of biomacromolecules is determined by its structure, which sets the foundation for its interaction with other molecules. By mimicking the natural system, we found that formation of disulfide bond give a great platform to form artificial assembled structure for multivalent interaction with bio-macromolecules. Although disulfide bond would be dissociated in intracellular reductive environment, elevated oxidative agents around mitochondria in senescent cells catalyzed formation of disulfide bond between building blocks. As the formation of disulfide bond increase hydrophobicity, the resultant oligomers assembled into spherical structure inside mitochondria. Thereby, assembled structures interact with mitochondrial membrane via multivalent interaction for inducing dysfunction of mitochondria, leading to apoptosis of senescent cells specifically. This polymerization shows great potential for senolytic treatment with selective removal of senescent cells.