Mechanisms and therapeutic implications of ferritinophagy in fibrotic diseases (Review)
7 affiliations
- 1School of Optometry, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
- 2Department of Orbital Diseases and Ocular Oncology, Jiangxi Research Institute of Ophthalmology and Visual Science, Nanchang, Jiangxi 330006, P.R. China
- 3Department of Orthopedics Surgery, People's Hospital of Yichun City, Yichun, Jiangxi 336000, P.R. China
- 4Department of Orthopedics Surgery, Yichun Affiliated Hospital, Nanchang University, Yichun, Jiangxi 336000, P.R. China
- 5Department of Orbital Diseases and Ocular Oncology, Jiangxi Clinical Research Center for Ophthalmic Disease, Nanchang, Jiangxi 330006, P.R. China
- 6Jiangxi Provincial Key Laboratory for Ophthalmology, Nanchang, Jiangxi 330006, P.R. China
- 7Department of Orbital Diseases and Ocular Oncology, National Clinical Research Center for Ocular Diseases, Nanchang, Jiangxi 330006, P.R. China
Abstract
Iron homeostasis depends on the coordinated regulation of iron uptake, storage, utilization and export to maintain cellular metabolism and redox balance. Ferritinophagy is an iron-specific form of autophagy mediated by the selective cargo receptor nuclear receptor coactivator 4. By delivering ferritin to the autophagy-lysosome system for degradation and releasing Fe2+, ferritinophagy regulates the intracellular labile iron pool and influences reactive oxygen species generation, lipid peroxidation and the ferroptosis threshold. Fibrosis is an aberrant repair response driven by chronic injury and is characterized by persistent inflammation, fibroblast activation and excessive extracellular matrix deposition. Increasing evidence has indicated that iron deposition and iron metabolic reprogramming are common features across a number of fibrotic disorders. Oxidative stress resulting from disrupted iron homeostasis can interact with the TGF-β signaling network to promote tissue remodeling. As an upstream regulatory mechanism, ferritinophagy may connect abnormal iron metabolism, oxidative stress, ferroptosis and profibrotic signaling through modulation of bioavailable iron, with bidirectional effects depending on cell type and disease stage. The present review summarizes the molecular basis and regulatory networks of ferritinophagy, whilst integrating recent advances regarding its role in fibrosis across different tissues or organs. It further discusses the potential balancing role of ferritinophagy in parenchymal cell injury and effector cell fate regulation, highlighting antifibrotic strategies targeting upstream metabolic regulation based on modulation of the ferroptosis threshold.
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BibTeX
@article{sun2026mechanisms,
title = {{Mechanisms and therapeutic implications of ferritinophagy in fibrotic diseases (Review)}},
author = {Siying Sun and Jie Yu and Xuemei Li and Hongfei Liao},
journal = {International Journal of Molecular Medicine},
year = {2026},
month = oct,
doi = {10.3892/ijmm.2026.6025},
url = {https://doi.org/10.3892/ijmm.2026.6025},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Mechanisms and therapeutic implications of ferritinophagy in fibrotic diseases (Review)
AU - Siying Sun
AU - Jie Yu
AU - Xuemei Li
AU - Hongfei Liao
PY - 2026
DA - 2026/10/23
JO - International Journal of Molecular Medicine
DO - 10.3892/ijmm.2026.6025
UR - https://doi.org/10.3892/ijmm.2026.6025
AB - Iron homeostasis depends on the coordinated regulation of iron uptake, storage, utilization and export to maintain cellular metabolism and redox balance. Ferritinophagy is an iron-specific form of autophagy mediated by the selective cargo receptor nuclear receptor coactivator 4. By delivering ferritin to the autophagy-lysosome system for degradation and releasing Fe2+, ferritinophagy regulates the intracellular labile iron pool and influences reactive oxygen species generation, lipid peroxidation and the ferroptosis threshold. Fibrosis is an aberrant repair response driven by chronic injury and is characterized by persistent inflammation, fibroblast activation and excessive extracellular matrix deposition. Increasing evidence has indicated that iron deposition and iron metabolic reprogramming are common features across a number of fibrotic disorders. Oxidative stress resulting from disrupted iron homeostasis can interact with the TGF-β signaling network to promote tissue remodeling. As an upstream regulatory mechanism, ferritinophagy may connect abnormal iron metabolism, oxidative stress, ferroptosis and profibrotic signaling through modulation of bioavailable iron, with bidirectional effects depending on cell type and disease stage. The present review summarizes the molecular basis and regulatory networks of ferritinophagy, whilst integrating recent advances regarding its role in fibrosis across different tissues or organs. It further discusses the potential balancing role of ferritinophagy in parenchymal cell injury and effector cell fate regulation, highlighting antifibrotic strategies targeting upstream metabolic regulation based on modulation of the ferroptosis threshold.
SN - 1107-3756
SN - 1791-244X
ER -