Plasma Membrane Rupture (PMR)

Plasma membrane rupture (PMR) is the final, cataclysmic step shared by several lytic forms of regulated cell death — secondary necrosis, pyroptosis, and likely ferroptosis (mediated by the protein NINJ1), as well as necroptosis (mediated by SIGLEC12). Both NINJ1 and SIGLEC12 use amphipathic helical motifs that insert into the plasma membrane once it comes under sufficient tension from cell swelling (oncosis), physically breaching it and releasing the cell’s remaining pro-inflammatory contents. Because it is the step that converts an already-dying cell into a full immunostimulatory event, PMR has been described as the “last message in a bottle” that amplifies immune signaling after cell death.