Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Jun 7;14(12):4035.
doi: 10.3390/jcm14124035.

Ferroptosis in Gastrointestinal Diseases: A New Frontier in Pathogenesis and Therapy

Adam Wawrzeńczyk  1 , Katarzyna Napiórkowska-Baran  1 , Ewa Alska  1 , Alicja Gruszka-Koselska  1 , Ewa Szynkiewicz  2 , Józef Sławatycki  3   4 , Paula Klemenska  3 , Zbigniew Bartuzi  1
Affiliations
Review

Ferroptosis in Gastrointestinal Diseases: A New Frontier in Pathogenesis and Therapy

Adam Wawrzeńczyk et al. J Clin Med. .

Abstract

Ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, has emerged as a key player in the pathogenesis of gastrointestinal (GI) diseases. Unlike apoptosis or necrosis, ferroptosis is characterized by distinctive metabolic and molecular pathways, including dysregulated iron metabolism, oxidative stress, and impaired antioxidant defenses. This review explores the complex role of ferroptosis in conditions such as inflammatory bowel disease (IBD), non-alcoholic steatohepatitis (NASH), and gastrointestinal cancers. Special attention is given to the molecular mechanisms underlying ferroptosis, including the Xc-/GSH/GPX4 axis, ferritinophagy, ACSL4/LPCAT3-mediated lipid remodeling, and the influence of the gut microbiota. Therapeutic strategies targeting ferroptosis-including pharmacological inhibitors, iron chelators, and microbiota-based interventions-are evaluated for their translational potential, underscoring ferroptosis as a promising target for precision therapies in gastroenterology and highlighting the need for further clinical studies to validate its diagnostic and therapeutic implications.

Keywords: GPX4; colorectal cancer; ferroptosis; gastrointestinal diseases; inflammatory bowel disease; iron metabolism; lipid peroxidation; liver disorders; oxidative stress; targeted therapy.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Summary of ferroptosis-associated gastrointestinal diseases. Definitions of abbreviations: HCC—hepatocellular carcinoma; NAFLD—non-alcoholic fatty liver disease; NASH—non-alcoholic steatohepatitis; ALD—alcoholic liver disease.
Figure 2
Figure 2
Fenton reaction.
Figure 3
Figure 3
Glutathione redox cycle.
Figure 4
Figure 4
The general mechanism of ferroptosis.
Figure 5
Figure 5
The general mechanism of ferritinophagy.
Figure 6
Figure 6
Therapeutics targets of ferroptosis.
See this image and copyright information in PMC

References

    1. Newton K., Strasser A., Kayagaki N., Dixit V.M. Cell death. Cell. 2024;187:235–256. doi: 10.1016/j.cell.2023.11.044. - DOI - PubMed
    1. Mou Y., Wang J., Wu J., He D., Zhang C., Duan C., Li B. Ferroptosis, a new form of cell death: Opportunities and challenges in cancer. J. Hematol. Oncol. 2019;12:34. doi: 10.1186/s13045-019-0720-y. - DOI - PMC - PubMed
    1. Wiredu Ocansey D.K., Yuan J., Wei Z., Mao F., Zhang Z. Role of ferroptosis in the pathogenesis and as a therapeutic target of inflammatory bowel disease. Int. J. Mol. Med. 2023;51:53. doi: 10.3892/ijmm.2023.5256. - DOI - PMC - PubMed
    1. Chen S., Zhu J.Y., Zang X., Zhai Y.Z. The Emerging Role of Ferroptosis in Liver Diseases. Front. Cell Dev. Biol. 2021;9:801365. doi: 10.3389/fcell.2021.801365. - DOI - PMC - PubMed
    1. Zhang X., Ma Y., Lv G., Wang H. Ferroptosis as a therapeutic target for inflammation-related intestinal diseases. Front. Pharmacol. 2023;14:1095366. doi: 10.3389/fphar.2023.1095366. - DOI - PMC - PubMed

LinkOut - more resources