An Analysis of AMPK and Ferroptosis in Cancer: A Potential Regulatory Axis

Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) is an energy homeostasis controller that regulates various metabolic pathways to promote adenosine triphosphate (ATP) generation and suppress energy expenditure, thereby restoring energy homeostasis. As a co-factor in many enzymes, iro...

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Main Authors: Ting Zhang, Xi Wang, Peter G Alexander, Peng Feng, Jianying Zhang
Format: Article
Language:English
Published: IMR Press 2025-07-01
Series:Frontiers in Bioscience-Landmark
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Online Access:https://www.imrpress.com/journal/FBL/30/7/10.31083/FBL36618
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author Ting Zhang
Xi Wang
Peter G Alexander
Peng Feng
Jianying Zhang
author_facet Ting Zhang
Xi Wang
Peter G Alexander
Peng Feng
Jianying Zhang
author_sort Ting Zhang
collection DOAJ
description Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) is an energy homeostasis controller that regulates various metabolic pathways to promote adenosine triphosphate (ATP) generation and suppress energy expenditure, thereby restoring energy homeostasis. As a co-factor in many enzymes, iron is an essential mineral for maintaining ATP levels in our bodies. Ferroptosis is an iron-dependent mode of cell death that occurs in various pathological processes, including cancer, metabolic disorders, and autoimmune diseases, by regulating iron metabolism, lipoperoxidation, and anti-oxidation functions. Ferroptosis is triggered by oxidative and energy stress, both controlled by cancer-associated signaling pathways. Emerging studies have demonstrated that AMPK directly influences ferroptosis by modulating lipid metabolism, redox homeostasis, and iron transport. Cancer cells exhibiting elevated baseline AMPK activity demonstrate resistance to ferroptosis, whereas AMPK suppression enhances their susceptibility to this regulated form of cell death. While the precise mechanistic details are yet to be fully elucidated, accumulating evidence suggests that AMPK-mediated ferroptosis regulation may contribute to cancer development and therapeutic responses. This review summarizes recent advances in understanding the interplay between AMPK and ferroptosis in cancer biology and discusses the potential of targeting the AMPK-ferroptosis axis for innovative anticancer strategies.
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series Frontiers in Bioscience-Landmark
spelling doaj-art-05a2b19ff15142099f1a4b4352f22dda2025-08-20T04:02:13ZengIMR PressFrontiers in Bioscience-Landmark2768-67012025-07-013073661810.31083/FBL36618S2768-6701(25)01667-3An Analysis of AMPK and Ferroptosis in Cancer: A Potential Regulatory AxisTing Zhang0Xi Wang1Peter G Alexander2Peng Feng3Jianying Zhang4Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Trauma Orthopedics, The First Affiliated Hospital of Xinjiang Medical University, 830011 Urumqi, Xinjiang, ChinaDepartment of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USAAdenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) is an energy homeostasis controller that regulates various metabolic pathways to promote adenosine triphosphate (ATP) generation and suppress energy expenditure, thereby restoring energy homeostasis. As a co-factor in many enzymes, iron is an essential mineral for maintaining ATP levels in our bodies. Ferroptosis is an iron-dependent mode of cell death that occurs in various pathological processes, including cancer, metabolic disorders, and autoimmune diseases, by regulating iron metabolism, lipoperoxidation, and anti-oxidation functions. Ferroptosis is triggered by oxidative and energy stress, both controlled by cancer-associated signaling pathways. Emerging studies have demonstrated that AMPK directly influences ferroptosis by modulating lipid metabolism, redox homeostasis, and iron transport. Cancer cells exhibiting elevated baseline AMPK activity demonstrate resistance to ferroptosis, whereas AMPK suppression enhances their susceptibility to this regulated form of cell death. While the precise mechanistic details are yet to be fully elucidated, accumulating evidence suggests that AMPK-mediated ferroptosis regulation may contribute to cancer development and therapeutic responses. This review summarizes recent advances in understanding the interplay between AMPK and ferroptosis in cancer biology and discusses the potential of targeting the AMPK-ferroptosis axis for innovative anticancer strategies.https://www.imrpress.com/journal/FBL/30/7/10.31083/FBL36618ampkferroptosiscancerenergy metabolismiron homeostasis
spellingShingle Ting Zhang
Xi Wang
Peter G Alexander
Peng Feng
Jianying Zhang
An Analysis of AMPK and Ferroptosis in Cancer: A Potential Regulatory Axis
Frontiers in Bioscience-Landmark
ampk
ferroptosis
cancer
energy metabolism
iron homeostasis
title An Analysis of AMPK and Ferroptosis in Cancer: A Potential Regulatory Axis
title_full An Analysis of AMPK and Ferroptosis in Cancer: A Potential Regulatory Axis
title_fullStr An Analysis of AMPK and Ferroptosis in Cancer: A Potential Regulatory Axis
title_full_unstemmed An Analysis of AMPK and Ferroptosis in Cancer: A Potential Regulatory Axis
title_short An Analysis of AMPK and Ferroptosis in Cancer: A Potential Regulatory Axis
title_sort analysis of ampk and ferroptosis in cancer a potential regulatory axis
topic ampk
ferroptosis
cancer
energy metabolism
iron homeostasis
url https://www.imrpress.com/journal/FBL/30/7/10.31083/FBL36618
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