Tag: Necroptosis

Programmed cell death (PCD) is a regulated biological process that eliminates damaged or unnecessary cells through apoptosis, autophagic cell death and regulated necrosis. By maintaining tissue homeostasis and supporting stress adaptation, PCD is essential for development and long‑term organismal health.

Necroptosis is a regulated necrotic cell‑death pathway driven by RIPK1–RIPK3–MLKL signalling. Through membrane permeabilisation and inflammatory activation, necroptosis eliminates infected or damaged cells when apoptosis is blocked, shaping immunity and disease progression.

RIPK1 is a central signalling kinase that determines whether a cell survives, undergoes apoptosis or triggers necroptosis. Through context‑dependent interactions with TNFR1, caspase‑8, RIPK3 and MLKL, RIPK1 integrates inflammatory cues and stress signals to regulate cell fate.

RIPK3 is a central necroptotic kinase that phosphorylates MLKL and drives regulated necrotic cell death. Through necrosome formation with RIPK1 and activation of inflammatory signalling, RIPK3 shapes immunity, tissue injury and disease progression.

MLKL is the terminal effector of necroptosis. After phosphorylation by RIPK3, MLKL oligomerises and inserts into the plasma membrane, causing membrane rupture and release of inflammatory DAMPs. MLKL is essential for regulated necrotic cell death and immune activation.