Fig. 7: The hypothetical model for STING-regulated macrophage ferroptosis promotes sepsis-induced intestinal injury via its interaction with NCOA4. | Cell Death & Disease

Fig. 7: The hypothetical model for STING-regulated macrophage ferroptosis promotes sepsis-induced intestinal injury via its interaction with NCOA4.

From: The interaction between STING and NCOA4 exacerbates lethal sepsis by orchestrating ferroptosis and inflammatory responses in macrophages

Fig. 7

In sepsis, STING can trigger ferroptosis through direct interaction with NCOA4 to induce ferritinophagy. Mechanistically, the CBD of STING directly binds the CC domain of NCOA4, which further enhances the stability of the STING dimer and lessens the protective effects of NCOA4 as a nuclear coactivator, decreasing the nuclear localization of NCOA4. These lead to macrophage ferroptosis and further promote sepsis-induced intestinal injury. In addition, we identified potential compounds targeting STING-induced ferroptosis, which could mitigate the induction of ferroptosis and STING activation in patients and septic mice. Created with BioRender.com.

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