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Cell pyroptosis is mediated by inflammasome and gasdermin D

Evavold et al.,Cell 2021

The process of pyroptosis is mediated by inflammasome and a downstream effector gasdermin D (GSDMD). Upon cleavage by inflammasome-associated caspases, the N-terminal domain of GSDMD forms membrane pores that promote cytolysis. We have shown that the Ragulator-Rag-mTORC1 pathway is required for pyroptosis induced by gasdermin D. Ragulator-Rag promotes reactive oxygen species production in macrophages, which in turn promote gasdermin D oligomerization, pore formation, and pyroptosis. These findings reveal an unexpected link between key regulators of immunity (inflammasome-GSDMD) and metabolism (Ragulator-Rag).

The study was done in collaboration between Boston Children’s Hospital, Harvard Medical School and National Institute of Chemistry.

Article: Evavold, Charles L., HAFNER BRATKOVIČ, Iva, Devant, Pascal, Dʼandrea, Jasmin M., Ngwa, Elsy M., BORŠIĆ, Elvira, Doench, John G., Lafleur, Martin W., Sharpe, Arlene H., Thiagarajah, Jay R., Kagan, Jonathan C. Control of gasdermin D oligomerization and pyroptosis by the Ragulator-Rag-mTORC1 pathway. Cell. 2021, 184, 4495-4511.

DOI: https://doi.org/10.1016/j.cell.2021.06.028

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