Red light activatable chemo-optogenetic dimerization regulates cell apoptosis

We report a non-phototoxic and non-photobleaching chemo-optogenetic dimerizer that effectively regulates protein-protein proximity inside living cells using far-red light. This system introduced the first deep-red/NIR light photoactivatable chemical inducer of proximity (pCIP) or dimerization (pCID), called dmBODIPY-ABA, or dmBODIPY caged abscisic acid (ABA). dmBODIPY-ABA dimerizer shows an anti-Stokes feature that further shifts the absorption to NIR direction and it displays a strong hyperchromic shift compared to the dmBODIPY photocage. By utilizing this non-invasive and biocompatible system, we successfully controlled apoptosis by targeting the key apoptotic factor, Bax, to the outer membrane of mitochondria, thus opening a window for precise control of programmed cancer cell death using deep-red light.