Details

Autor(en) / Beteiligte

• Flores‐Romero, Hector
• Ros, Uris
• Garcia‐Saez, Ana J

Titel

Pore formation in regulated cell death

Ist Teil von

• The EMBO journal, 2020-12, Vol.39 (23), p.e105753-n/a

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2020

Quelle

Access via Wiley Online Library

Beschreibungen/Notizen

• 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. Graphical Abstract In this review, Ana Garcia‐Saez and colleagues compare and contrast the mechanisms by which proteins such as BAX/BAK, Gasdermins and MLKL can create membrane pores, and which roles these play, in different forms of regulated cell death.