Ferritinophagy/ferroptosis: Iron-related newcomers in human diseases.

Abstract

Nuclear receptor coactivator 4 mediated ferritinophagy is an autophagic phenomenon that specifically involves ferritin to release intracellular free iron. Ferritinophagy is implicated in maintaining efficient erythropoiesis. Notably, ferritinophagy also plays a central role in driving some pathological processes, including Parkinson's disease (PD) and urinary tract infections. Some evidence has demonstrated that ferritinophagy is critical to induce ferroptosis. Ferroptosis is a newly nonapoptotic form of cell death, characterized by the accumulation of iron-based lipid reactive oxygen species. Ferroptosis plays an important role in inhibiting some types of cancers, such as hepatocellular carcinoma, pancreatic carcinoma, prostate cancer, and breast cancer. Conversely, the activation of ferroptosis accelerates neurodegeneration diseases, including PD and Alzheimer's disease. Therefore, in this review, we summarize the regulatory mechanisms related to ferritinophagy and ferroptosis. Moreover, the distinctive effects of ferritinophagy in human erythropoiesis and some pathologies, coupled with the promotive or inhibitory role of tumorous and neurodegenerative diseases mediated by ferroptosis, are elucidated. Obviously, activating or inhibiting ferroptosis could be exploited to achieve desirable therapeutic effects on diverse cancers and neurodegeneration diseases. Interrupting ferritinophagy to control iron level might provide a potentially therapeutic avenue to suppress urinary tract infections.

• Authors: Mingzhu Tang, Zhe Chen, Di Wu, Linxi Chen
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 233 Issue 12 Pg. 9179-9190 (12 2018) ISSN: 1097-4652 [Electronic] United States
• PMID: 30076709 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• NCOA4 protein, human
• Nuclear Receptor Coactivators
• Reactive Oxygen Species
• Ferritins
• Iron

Topics

• Autophagy (genetics)
• Erythropoiesis (genetics)
• Ferritins (adverse effects, metabolism)
• Humans
• Iron (metabolism)
• Iron Metabolism Disorders (genetics, metabolism, pathology)
• Neoplasms (classification, etiology, metabolism, pathology)
• Neuroaxonal Dystrophies (genetics, metabolism, pathology)
• Nuclear Receptor Coactivators (genetics)
• Parkinson Disease (genetics, metabolism)
• Reactive Oxygen Species (metabolism)
• Urinary Tract Infections (genetics, metabolism)