Fig. 8 | Signal Transduction and Targeted Therapy

Fig. 8

From: Disruption of heme homeostasis by nuclear receptor Nur77 induces pyroptosis through granzyme B-dependent GSDMC cleavage

Fig. 8

Working model for the DdBIC function. DdBIC directly targets the nuclear receptor Nur77. With the assistance of HK2, Nur77 is translocated into the mitochondria to negatively regulate the heme level by increasing the activity of SDHA, which causes leakage of electrons, leading to increased mito-ROS. The mitochondrial protease OMA1 senses this ROS signal via oxidation and then cleaves its downstream OPA1, which converts OPA1 into S-OPA1 that subsequently releases into the cytoplasm. Cytosolic S-OPA1 activates PERK to cause an integrated stress response (ISR) and then activates granzyme B activity, which further cleaves GSDMC and induces pyroptosis. Figure 8, created using BioRender.com

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