The liquid-liquid phase separation in programmed cell death

Cell Signal. 2024 May 11:120:111215. doi: 10.1016/j.cellsig.2024.111215. Online ahead of print.

Abstract

In recent years, the physical phenomenon of liquid-liquid phase separation has been widely introduced into biological research. Membrane-free organelles have been found to exist in cells that were driven by liquid-liquid phase separation. Intermolecular multivalent interactions can drive liquid-liquid phase separation to form condensates that are independent of other substances in the environment and thus can play an effective role in regulating multiple biological processes in the cell. The way of cell death has also long been a focus in multiple research. In the face of various stresses, cell death-related mechanisms are crucial for maintaining cellular homeostasis and regulating cell fate. With the in-depth study of cell death pathways, it has been found that the process of cell death was also accompanied by the regulation of liquid-liquid phase separation and played a key role. Therefore, this review summarized the roles of liquid-liquid phase separation in various cell death pathways, and explored the regulation of cell fate by liquid-liquid phase separation, with the expectation that the exploration of the mechanism of liquid-liquid phase separation would provide new insights into the treatment of diseases caused by regulated cell death.

Keywords: Apoptosis; Autophagy; Ferroptosis; Liquid-liquid phase separation; Programmed cell death; Pyroptosis.