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. Author manuscript; available in PMC: 2023 Jan 18.
Published in final edited form as: Cell. 2021 Aug 19;184(17):4374–4376. doi: 10.1016/j.cell.2021.07.036

Figure 1. The Ragulator-Rag-mTORC1 pathway promotes GSDMD oligomerization and pore formation.

Figure 1.

Upon inflammasome stimulation, activated inflammatory caspases process GSDMD into NT-GSDMD and CT-GSDMD. NT-GSDMD translocates to plasma membrane and oligomerizes to form pores that mediate cytokine secretion and pyroptotic cell death. The Ragulator-Rag-mTORC1 pathway at the lysosomal membrane regulates ROS production in mitochondria that promotes the oligomerization and pore formation by NT-GSDMD. Deficiency or inhibition of Rag proteins or mTORC1 components diminishes NT-GSDMD-mediated pore formation and cytolysis. The Ragulator-Rag complex also regulates pyroptosis upstream of GSDMD cleavage through caspase-8 activation.