Ferroptosis Is a Potential Therapeutic Target for Pulmonary Infectious Diseases

Figure 3

The cascade of these substances during infection. The PA without AA-PE produces pLoxA, which converts AA-PE contained in human bronchial epithelial cells into 15-HOO-AA-PE and produces ROS. MTB infection induces a decrease in GPX4 levels and an increase in LPO, free iron, and ROS. SARS-CoV-2 inhibits GPX4 expression. In addition, ROS can be produced and lipid peroxidation can be promoted to generate LPO during Staphylococcus aureus infection. Also, ROS are also produced during Klebsiella pneumoniae infection. Meanwhile, Leishmania spp infection of GPX4-deficient T lymphocytes causes LPO accumulation. A decrease in GPX4 levels weakens its ability to break down LPO, leading to the accumulation of LPO. Additionally, ROS can also produce LPO through lipid peroxidation. Meanwhile, the increase of free iron leads to the increase of oxygen free radical produced by Fenton reaction. Both LPO and hydroxyl radicals can damage cells and eventually lead to ferroptosis. PA: Pseudomonas aeruginosa; AA-PE: arachidonic acid-phosphatidyl ethanolamine; pLoxA: lipoxygenase; 15-HOO-AA-PE: 15-hydrogenation oxygen-AAPE; ROS: reactive oxygen species; MTB: Mycobacterium tuberculosis; LPO: lipid peroxides; SARS-CoV-2: severe acute respiratory syndrome coronavirus type 2; GPX4: glutathione peroxidase 4.