Role of Ferroptosis in Lung Diseases

Abstract

Ferroptosis is a new type of programmed cell death characterized by intracellular iron accumulation and lipid peroxidation that leads to oxidative stress and cell death. The metabolism of iron, lipids, and amino acids and multiple signalling pathways precisely regulate the process of ferroptosis. Emerging evidence has demonstrated that ferroptosis participates in the occurrence and progression of various pathological conditions and diseases, such as infections, neurodegeneration, tissue ischaemia-reperfusion injury and immune diseases. Recent studies have also indicated that ferroptosis plays a critical role in the pathogenesis of acute lung injury, chronic obstructive pulmonary disease, pulmonary fibrosis, pulmonary infection and asthma. Herein, we summarize the latest knowledge on the regulatory mechanism of ferroptosis and its association with iron, lipid and amino acid metabolism as well as several signalling pathways. Furthermore, we review the contribution of ferroptosis to the pathogenesis of lung diseases and discuss ferroptosis as a novel therapeutic target for various lung diseases.

Keywords: ferroptosis; lung diseases; metabolic networks and pathways; signalling pathways.

Figure 1

Regulatory pathways of ferroptosis. The figure shows the regulatory pathways of ferroptosis, which can be roughly divided into two categories: the first category involves metabolic pathways associated with ferroptosis, such as abnormal iron, lipid and amino acid pathways; the second category involves signalling pathways associated with ferroptosis, such as the p53, nuclear factor erythroid 2-related factor 2, heat shock proteins, haem oxygenase-1, nuclear receptor coactivator 4 and mevalonate pathways. In addition, erastin acts on multiple pathways to induce ferroptosis.