Figure 1. Prevention of necroptosis by ESCRT-III-mediated plasma membrane repair.

During necroptosis in kidney transplants, ischemia-reperfusion injury causes formation of the necrosome, a higher order complex that contains RIPK3. This kinase phosphorylates MLKL to signal necroptosis through mechanisms that include translocation to the plasma membrane. Damaged parts of the plasma membrane, identified though of unknown origin, are shed in the forms of bubbles from the plasma membrane to maintain its integrity on the expense of bubbles that are secreted from the cell. This mechanism depends on ESCRT-III and provides time to the dying cell. It is hypothesized that this extension until death is useful for the de novo generation of immunomodulatory cytokines, such as CXCL1, IL-33 and IL-1β.