The molecular mechanism of ferroptosis and its role in COPD

Abstract

Ferroptosis, a new type of cell death, is mainly characterized by intracellular iron accumulation and lipid peroxidation. The complex regulatory network of iron metabolism, lipid metabolism, amino acid metabolism, p53-related signaling, and Nrf2-related signaling factors is involved in the entire process of ferroptosis. It has been reported that ferroptosis is involved in the pathogenesis of neurological diseases, cancer, and ischemia-reperfusion injury. Recent studies found that ferroptosis is closely related to the pathogenesis of COPD, which, to some extent, indicates that ferroptosis is a potential therapeutic target for COPD. This article mainly discusses the related mechanisms of ferroptosis, including metabolic regulation and signaling pathway regulation, with special attention to its role in the pathogenesis of COPD, aiming to provide safe and effective therapeutic targets for chronic airway inflammatory diseases.

Keywords: COPD; ferroptosis; inflammation; iron; lipid peroxidation.

Figure 1

Main regulatory pathways of ferroptosis. There are two main ways of regulating ferroptosis shown in the figure: the first is the pathway of abnormal iron, amino acid, and lipid metabolism; the second involves the related signaling pathways that regulate ferroptosis, such as the P53 and Nrf2 pathways. Glu, glutamic acid; GSH, glutathione; GPX4, glutathione peroxidase 4; Nrf2, Nuclear factor erythroid 2-related factor 2; GLS2, glutaminase 2; LOXs, lipoxygenases; ROS, reactive oxygen species; DMT1, divalent metal ion transporter-1; SAT1, spermidine N1-acetyltransferase 1; TfR, transferrin receptor.

Figure 2

Possible relationship between ferroptosis and COPD, ROS, CS, and PM2.5 trigger COPD, resulting in an inflammatory reaction and abnormal levels of inflammatory factors. Conversely, abnormal inflammatory factors can aggravate COPD, Nrf2 can inhibit the production of reactive oxygen species and iron and the occurrence of COPD and ferroptosis. A direct link between ferroptosis and COPD remains unclear. Nrf2, Nuclear factor erythroid 2-related factor 2; CS, cigarette smoke; ROS, reactive oxygen species; AP-1, activator protein 1; NF-κB, nuclear factor of kappa B.