Optogenetic Control of Non-Apoptotic Cell Death.
                            
                                blue
                            
                            
                                cpLOV2
                            
                                cpLOVTRAP
                            
                                CRY2/CRY2
                            
                                LOVTRAP
                            
                            
                                
                                    786-O
                                
                            
                                
                                    B16-F0
                                
                            
                                
                                    E. coli
                                
                            
                                
                                    HEK293T
                                
                            
                                
                                    HeLa
                                
                            
                                
                                    Jurkat
                                
                            
                            
                                Signaling cascade control
                            
                                Cell death
                            
                            
                            
                            
                            
                        
                        
                        
                        
                            Abstract:
                            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.