A translation factor gets cleaved during apoptosis (left), but remains intact during necrosis (right).

Necrosis, unlike its well-studied sister apoptosis, remains largely a black box. Evidence exists for a programmed necrosis pathway, but what happens between the initial signaling events and cell rupture is largely unknown. Now, Saelens et al. (on page 545) report that during necrosis protein synthesis continues until the integrity of the cell membrane is lost.

Early in apoptosis, caspase-mediated cleavage of the translation initiation factors rapidly shuts off protein synthesis. Sure enough, if cells underwent apoptosis then protein synthesis was rapidly extinguished, as detected by 35S-methionine labeling experiments, regardless of the cell death trigger used. In contrast, protein synthesis continued in cells that underwent necrotic death, until the cell ruptured. Furthermore, translation initiation factors remained intact during necrotic death.

Continued protein synthesis after the initiation of cell death may allow nonenveloped viruses, which can trigger necrosis, to coopt the available translation machinery for their own nefarious uses. It may also, however, provide a cell with a mechanism to alert its neighbors to trouble. The researchers are currently using proteomics to see whether the types of messages that are being translated change after cell death starts.