Optogenetic activators of apoptosis, necroptosis, and pyroptosis

Area of Science:

• Cell biology
• Genetics
• Biotechnology

Background:

• Controlled induction of cell death is crucial for understanding tissue and organism responses.
• Existing methods for inducing cell death lack precision and specificity.
• Optogenetics offers a powerful approach for spatiotemporal control of biological processes.

Purpose of the Study:

• To develop novel optogenetic tools for precise induction of programmed cell death (PCD).
• To enable light-mediated control over apoptosis, pyroptosis, and necroptosis.
• To investigate cellular responses to different modes of cell death.

Main Methods:

• Development of optogenetically controlled cell death effectors (optoCDEs) utilizing Arabidopsis thaliana Cryptochrome-2.
• Application of optoCDEs in human, mouse, and zebrafish cell lines for inducing PCD.
• Utilizing optoCDEs for in vitro and in vivo experiments, including single-cell elimination.
• Assessing neighboring cell responses to apoptotic versus necrotic cell death.

Main Results:

• OptoCDEs successfully induced rapid and specific PCD (apoptosis, pyroptosis, necroptosis) in multiple cell types.
• The tools demonstrated suitability for sub-lethal cell death induction and precise elimination of cells.
• Proof-of-concept experiments revealed distinct neighboring cell responses to apoptotic and necrotic cell death.
• A novel role for sphingosine-1-phosphate signaling in efferocytosis of apoptotic cells by epithelia was identified.

Conclusions:

• OptoCDEs represent a novel class of optogenetic tools for precise control of programmed cell death.
• These tools offer broad applicability in studying cell death mechanisms and cellular responses.
• The findings highlight the potential of optogenetics in advancing cell biology research and therapeutic strategies.