Fig. 4: The role of NF-κB signaling pathway in ferroptosis.
From: The interaction between ferroptosis and inflammatory signaling pathways
The classical signaling pathway is activated by Toll‑like receptor ligands (such as LPS), TNF, IL-1, and other stimuli. Under resting conditions, IκBα combines with NF-κB dimers to sequester NF-κB activity. These signaling molecules combine with their corresponding receptors and mediate the phosphorylation and subsequent degradation of IκBα. Then, the liberated NF-κB dimers are translocated to the nucleus and regulate target gene transcription. On the one hand, NF-κB can reduce the transcription of antioxidant molecules, such as GPX4, NQO1, and HMOX1, indicating the contribution of the NF-κB pathway to oxidative stress. On the other hand, the loss of LIFR enhances IκBα ubiquitination degradation and positively regulates NF-κB activation, which further promotes LCN2 secretion to sequester extracellular iron. In addition, a few agents, including BRD4770 and BAY 11-7082, exert their anti-ferroptosis effects via inhibiting NF-κB pathway.
