Regulation of iron metabolism in ferroptosis: From mechanism research to clinical translation.

Xin ZHANG; Yang XIANG; Qingyan WANG; Xinyue BAI; Dinglun MENG; Juan WU; Keyao SUN; Lei ZHANG; Rongrong QIANG; Wenhan LIU; Xiang ZHANG; Jingling QIANG; Xiaolong LIU; Yanling YANG

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Regulation of iron metabolism in ferroptosis: From mechanism research to clinical translation.

Author: Xin ZHANG ¹ ; Yang XIANG ² ; Qingyan WANG ¹ ; Xinyue BAI ¹ ; Dinglun MENG ¹ ; Juan WU ³ ; Keyao SUN ¹ ; Lei ZHANG ¹ ; Rongrong QIANG ¹ ; Wenhan LIU ¹ ; Xiang ZHANG ¹ ; Jingling QIANG ⁴ ; Xiaolong LIU ¹ ; Yanling YANG ¹
Author Information

1. Yan'an Medical College of Yan'an University, Yan'an, Shaanxi, 716000, China.
2. College of Physical Education, Yan'an University, Yan'an, Shaanxi, 716000, China.
3. Xi'an Central Hospital, Xi'an, 710000, China.
4. Department of Neurosurgery, Affiliated Hospital of Yan'an University, Yan'an, Shaanxi, 716000, China.
Publication Type:Review
Keywords: Clinical translation; Ferroptosis; Iron metabolism; Iron regulators
From: Journal of Pharmaceutical Analysis 2025;15(10):101304-101304
CountryChina
Language:English
Abstract: Iron is an essential trace element in the human body, crucial in maintaining normal physiological functions. Recent studies have identified iron ions as a significant factor in initiating the ferroptosis process, a novel mode of programmed cell death characterized by iron overload and lipid peroxide accumulation. The iron metabolism pathway is one of the primary mechanisms regulating ferroptosis, as it maintains iron homeostasis within the cell. Numerous studies have demonstrated that abnormalities in iron metabolism can trigger the Fenton reaction, exacerbating oxidative stress, and leading to cell membrane rupture, cellular dysfunction, and damage to tissue structures. Therefore, regulation of iron metabolism represents a key strategy for ameliorating ferroptosis and offers new insights for treating diseases associated with iron metabolism imbalances. This review first summarizes the mechanisms that regulate iron metabolic pathways in ferroptosis and discusses the connections between the pathogenesis of various diseases and iron metabolism. Next, we introduce natural and synthetic small molecule compounds, hormones, proteins, and new nanomaterials that can affect iron metabolism. Finally, we provide an overview of the challenges faced by iron regulators in clinical translation and a summary and outlook on iron metabolism in ferroptosis, aiming to pave the way for future exploration and optimization of iron metabolism regulation strategies.