Molecular mechanisms of ferroptosis and relevance to inflammation

Abstract

Introduction Inflammation is a defensive response of the organism to irritation which is manifested by redness, swelling, heat, pain and dysfunction. The inflammatory response underlies the role of various diseases. Ferroptosis, a unique modality of cell death, driven by iron-dependent lipid peroxidation, is regulated by multifarious cellular metabolic pathways, including redox homeostasis, iron processing and metabolism of lipids, as well as various signaling pathways associated with diseases. A growing body of evidence suggests that ferroptosis is involved in inflammatory response, and targeting ferroptosis has great prospects in preventing and treating inflammatory diseases. Materials and methods Relevant literatures on ferroptosis, inflammation, inflammatory factors and inflammatory diseases published from January 1, 2010 to now were searched in PubMed database. Conclusion In this review, we summarize the regulatory mechanisms associated with ferroptosis, discuss the interaction between ferroptosis and inflammation, the role of mitochondria in inflammatory ferroptosis, and the role of targeting ferroptosis in inflammatory diseases. As more and more studies have confirmed the relationship between ferroptosis and inflammation in a wide range of organ damage and degeneration, drug induction and inhibition of ferroptosis has great potential in the treatment of immune and inflammatory diseases.

Interaction between ferroptosis and TNF‐α: Impact in obesity‐related osteoporosis

“…Recently, increasing studies have suggested that proinflammatory cytokines serve as the connection between ferroptosis and inflammation 37,38 . TNF‐α can be implicated in the process of ferroptosis through regulating GSH and iron metabolism 39–41 .…”

“…While, TNF‐α triggers ferroptosis of keratinocytes through promoting the accumulation of ROS, MDA, and iron 44 . It is well established that ferroptosis aggregates inflammation through the release of proinflammatory molecules 37 . Ferroptosis is often accompanied by increased serum levels of TNF‐α 37 .…”

Editorial: Ferroptosis as a novel therapeutic target for inflammation-related diseases

“…Ferroptosis is accompanied by the release of proinflammatory molecules, such as interleukin (IL)-1β and IL-18 ( Sun et al, 2020 ). Meanwhile, ferroptosis exacerbates the inflammatory response to varying degrees through mediators such as ferroptosis regulators like glutathione peroxidase 4, reactive oxygen species, lipoxygenases, and inflammatory mediators produced during ferroptosis ( Deng et al, 2022 ). Several anti-inflammatory drugs have been shown to inhibit ferroptosis in certain cellular models ( Wang et al, 2023 ).…”

“…Many inflammatory diseases are associated with ferroptosis, such as acute renal failure, Acute lung injury, neurodegenerative diseases, chronic autoimmune diseases of the gastrointestinal, etc. ( Deng et al, 2022 ). A review by Zhang et al reported that inflammatory-associated intestinal diseases are strongly associated with ferroptosis, indicating that ferroptosis may act as potential therapeutic targets for inflammatory-associated intestinal diseases.…”

Editorial: Liver diseases and programmed cell death

“…Several publications have reported that ferroptosis is associated with liver disease ( Wu et al, 2021 ; Luo et al, 2021 ). The underlying mechanisms may be related to inflammatory responses, too ( Deng et al, 2022 ). The present Research Topic is comprised of five primary articles and three evaluations that center on the Research Topic of PCD.…”