학술논문

Pore formation in regulated cell death.
Document Type
Article
Source
EMBO Journal. Dec2020, Vol. 39 Issue 23, p1-18. 18p.
Subject
*CELL death
*CELL membranes
*CELL determination
*MEMBRANE permeability (Biology)
*APOPTOSIS
Language
ISSN
0261-4189
Abstract
The discovery of alternative signaling pathways that regulate cell death has revealed multiple strategies for promoting cell death with diverse consequences at the tissue and organism level. Despite the divergence in the molecular components involved, membrane permeabilization is a common theme in the execution of regulated cell death. In apoptosis, the permeabilization of the outer mitochondrial membrane by BAX and BAK releases apoptotic factors that initiate the caspase cascade and is considered the point of no return in cell death commitment. Pyroptosis and necroptosis also require the perforation of the plasma membrane at the execution step, which involves Gasdermins in pyroptosis, and MLKL in the case of necroptosis. Although BAX/BAK, Gasdermins and MLKL share certain molecular features like oligomerization, they form pores in different cellular membranes via distinct mechanisms. Here, we compare and contrast how BAX/BAK, Gasdermins, and MLKL alter membrane permeability from a structural and biophysical perspective and discuss the general principles of membrane permeabilization in the execution of regulated cell death. [ABSTRACT FROM AUTHOR]