Arsenite-induced necroptosis requires stress granules

Abstract

Oxidative stress can trigger a type of programmed cell death called necroptosis. According to a new study, the environmental pollutant arsenite can induce necroptosis, but the process requires the presence of stress granules—subcellular domains that store stalled translation machinery in stressed cells ( Sci. Signal. 2023, DOI: 10.1126/scisignal.abq0837 ). Although stress granules are necessary for arsenite-induced necroptosis, their formation isn’t enough to trigger the process. Two other proteins—Z-DNA-binding protein 1 (ZBP1) and receptor-interacting protein kinase 3 (RIPK3)—are also required. Without ZBP1, the cells can’t sense that they need to start the process of necroptosis, says Arizona State University virologist Bertram L. Jacobs, who led the team that carried out the study. But most cells, including the ones used in the study, don’t normally produce ZBP1. The team used interferon, a protein associated with inflammation, to induce the production of ZBP1. How the need for interferon plays out in contexts other