Emerging roles of ferroptosis in pulmonary fibrosis: current perspectives, opportunities and challenges

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: June 24, 2024

Abstract Pulmonary fibrosis (PF) is a chronic interstitial lung disorder characterized by abnormal myofibroblast activation, accumulation of extracellular matrix (ECM), and thickening fibrotic alveolar walls, resulting in deteriorated function. PF initiated dysregulated wound healing processes triggered factors such as excessive inflammation, oxidative stress, coronavirus disease (COVID-19). Despite advancements understanding the disease’s pathogenesis, effective preventive therapeutic interventions are currently lacking. Ferroptosis, an iron-dependent regulated cell death (RCD) mechanism involving lipid peroxidation glutathione (GSH) depletion, exhibits unique features distinct from other RCD forms (e.g., apoptosis, necrosis, pyroptosis). Imbalance between reactive oxygen species (ROS) production detoxification leads to ferroptosis, causing cellular dysfunction through peroxidation, protein modifications, DNA damage. Emerging evidence points crucial role ferroptosis progression, driving macrophage polarization, fibroblast proliferation, ECM deposition, ultimately contributing tissue scarring. This review provides comprehensive overview latest findings on involvement signaling mechanisms emphasizing potential novel anti-fibrotic approaches targeting for management.

Language: Английский

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Programmed cell death in nasopharyngeal carcinoma: Mechanisms and therapeutic targets

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: 1880(1), P. 189265 - 189265

Published: Jan. 13, 2025

Language: Английский

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Lysosomes finely control macrophage inflammatory function via regulating the release of lysosomal Fe2+ through TRPML1 channel

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 24, 2025

Lysosomes are best known for their roles in inflammatory responses by engaging autophagy to remove inflammasomes. Here, we describe an unrecognized role the lysosome, showing that it finely controls macrophage function manipulating lysosomal Fe2+—prolyl hydroxylase domain enzymes (PHDs)—NF-κB—interleukin 1 beta (IL1B) transcription pathway directly links lysosomes with responses. TRPML1, a cationic channel, is activated secondarily ROS elevation upon stimuli, which turn suppresses IL1B transcription, thus limiting excessive production of IL-1β macrophages. Mechanistically, suppression caused TRPML1 activation results from its modulation on release Fe2+, subsequently activates PHDs. The PHDs then represses transcriptional activity NF-κB, ultimately resulting suppressed transcription. More importantly, vivo stimulation ameliorates multiple clinical signs Dextran sulfate sodium-induced colitis mice, suggesting has potential treating bowel disease. via autophagy. Xing et al., find regulate controlling interleukin-1β production, altering Fe2+ through channel.

Language: Английский

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Programmed enhancement of endogenous iron-mediated lysosomal membrane permeabilization for tumor ferroptosis/pyroptosis dual-induction

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 28, 2025

Language: Английский

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Targeting lipid metabolism for ferroptotic cancer therapy

APOPTOSIS, Journal Year: 2022, Volume and Issue: 28(1-2), P. 81 - 107

Published: Nov. 18, 2022

Language: Английский

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