Quantitative and Repetitive Control of Subcellular Protein–Protein Interaction Using a Photochromic Dimerizer

Artificial control of intracellular protein dynamics with high precision provides deep insight into complicated biomolecular networks. Optogenetics and caged compound-based chemically induced dimerization (CID) systems are emerging as tools for spatiotemporally regulating intracellular protein dynamics. However, both technologies face several challenges for accurate control such as the duration of activation, deactivation rate, and repetition cycles. Herein, we report a photochromic CID system that employs the photoisomerization of a ligand so that both association and dissociation are controlled by light, enabling quick, repetitive, and quantitative regulation of the target protein localization upon violet and green light illumination. We also demonstrated the usability of the photochromic CID system as a potential tool to finely manipulate intracellular protein dynamics to study diverse cellular processes. Utilizing this system to manipulate PINK1/Parkin-mediated mitophagy, we showed that PINK1 recruitment to the mitochondria can promote Parkin recruitment to proceed with mitophagy.