Controllable mitochondrial regulation based on photo-triggered DNA circuitry†

DNA circuits have been widely used in the regulation of biomolecules and biochemical reactions due to their excellent controllability and responsiveness, but their regulation of intracellular organelles is still limited. Herein, we develop a photo-triggered mitochondrial regulation strategy based on a hybridization chain reaction (HCR) in living cells. In the design, the initial DNA hairpin is locked by a photocleavable group, and the assembling DNA hairpin pairs are tagged with triphenylphosphine for mitochondrial binding. Upon irradiation with UV light, the initiator hairpin is cleaved to trigger the HCR between triphenylphosphine-labeled hairpin pairs, followed by forming a long double-stranded DNA polymer for several of the mitochondria regulations in living cells. Our results demonstrate that mitochondrial regulation based on the HCR can successfully repair ROS stressed cells. Together, this work provides a new strategy for the spatiotemporally controlled regulation of intracellular mitochondria, exhibiting great potential in precision therapy.