Cell Death

Delaying demise

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Science  28 Apr 2017:
Vol. 356, Issue 6336, pp. 393-394
DOI: 10.1126/science.356.6336.393-f

The final insult during the mammalian cell death process called necroptosis is loss of membrane integrity. What happens next is uncontrolled release of cytoplasmic contents into the extracellular space. Gong et al. report that cells can delay this final step by recruiting cellular machinery to generate membrane buds. Execution of necroptosis involves the localization of an enzyme called MLKL (mixed lineage kinase domain-like) to the plasma membrane. MLKL recruits components of the endosomal sorting complexes required to transport ESCRT-III to the degrading membrane. ESCRT-III sustains membrane integrity by forming membrane blebs, which are eventually shed by the cell. Thus, ESCRT-III recruitment may buy time for the cell to signal to other cells before death. The work also indicates possible interventions to prevent cell death.

Cell 169, 286 (2017).

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