Optogenetic Control of Non-Apoptotic Cell Death

Herein, a set of optogenetic tools (designated LiPOP) that enable photoswitchable necroptosis and pyroptosis in live cells with varying kinetics, is introduced. The LiPOP tools allow reconstruction of the key molecular steps involved in these two non-apoptotic cell death pathways by harnessing the power of light. Further, the use of LiPOPs coupled with upconversion nanoparticles or bioluminescence is demonstrated to achieve wireless optogenetic or chemo-optogenetic killing of cancer cells in multiple mouse tumor models. LiPOPs can trigger necroptotic and pyroptotic cell death in cultured prokaryotic or eukaryotic cells and in living animals, and set the stage for studying the role of non-apoptotic cell death pathways during microbial infection and anti-tumor immunity.

Automated summary

LiPOP is a set of optogenetic tools that can induce photoswitchable necroptosis and pyroptosis in live cells using light. Studies have shown that combining LiPOPs with upconversion nanoparticles or bioluminescence can achieve wireless optogenetic or chemo-optogenetic killing of cancer cells in multiple mouse tumor models. LiPOPs have the potential to trigger necroptotic and pyroptotic cell death in cultured cells and living animals, opening up possibilities for studying non-apoptotic cell death pathways in microbial infection and anti-tumor immunity.