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Fig. 3 | Journal of Hematology & Oncology

Fig. 3

From: Ferroptosis, a new form of cell death: opportunities and challenges in cancer

Fig. 3

The regulatory network of ferroptosis. PHKG2, IREB2, and CISD1 play an important role in ferroptosis by their function in iron metabolism balance. The phosphorylation of HSP27 induces ferroptosis resistance through blocking cytoskeleton-mediated iron absorption. EGLN1 can upregulate LSH expression by limiting HIF 1α. LSH inhibits ferroptosis by affecting metabolism-associated genes including SCD1, GLUT1, and FADS2. Also, protein kinase C-mediated HSPB1 is a negative regulator of ferroptosis by inhibiting ROS production and reducing iron uptake. The p62-Keap1-Nrf2 pathway plays a vital role against ferroptosis by regulating Nrf2-targeted genes HO-1, FTH1, and NQO1. AMPK-mediated BECN1 phosphorylation and BAP1 directly represses system xc- activity, leading to the elevated ROS level and ferroptosis. MUC1-C binding with CD44v promotes the stability of system xc-. The inhibition of CDO1 restores the levels of GSH and increases ROS. Methionine can be converted to S-adenosylhomocysteine and Cys through the sulfur transfer pathway, which is essential for GPX4 biosynthesis. IPP and CoQ10 are the important products of the MVA pathway, which promotes GPX4 synthesis. FIN56 treatment also reduces CoQ10 by modulating SQS. VDAC2/3 and CARS are positive regulators of ferroptosis. ROS accumulation requires the activation of PUFAs by ACSL4 and LPCAT3. And LOX directly catalyzes the peroxidation of phospholipid PUFAs

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