NINJ1 mediates multiple lytic cell death pathways by controlling plasma membrane rupture and forms oligomeric assemblies. However, the precise mechanism by which NINJ1 assembles into higher order structures in the cell membrane and controls membrane rupture remains unclear. Here, we demonstrate that the activation of NINJ1 leads to redistribution of the protein from the liquid-disordered (Ld) phase to the interface between liquid-ordered (Lo) and Ld domains, thereby assembling into ring-like structures. These findings suggest a potential mechanism for NINJ1 assembly and provide a unified model for NINJ1-mediated membrane damage. Activated NINJ1 also represents one of the first protein linactants.
Yang et al. (Sun,) studied this question.