Emerging Roles of Energy Metabolism in Ferroptosis Regulation of Tumor Cells. Issue 22 (10th October 2021)

• Record Type: Journal Article
• Authors: Yao, Xuemei; Li, Wei; Fang, De; Xiao, Chuyu; Wu, Xiao; Li, Menghuan; Luo, Zhong
• Is Part Of: Advanced science. Volume 8:Issue 22(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-10-10
• Subjects: cellular energy metabolism -- ferroptosis -- glucose -- glutamine; Science -- Periodicals; 505
• DOI: 10.1002/advs.202100997
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: Ferroptosis is a new form of regulated cell death, which is characterized by the iron‐dependent accumulation of lethal lipid peroxides and involved in many critical diseases. Recent reports revealed that cellular energy metabolism activities such as glycolysis, pentose phosphate pathway (PPP), and tricarboxylic acid cycle are involved in the regulation of key ferroptosis markers such as reduced nicotinamide adenine dinucleotide phosphate (NADPH), glutathione (GSH), and reactive oxygen species (ROS), therefore imposing potential regulatory roles in ferroptosis. Remarkably, tumor cells can activate adaptive metabolic responses to inhibit ferroptosis for self‐preservation such as the upregulation of glycolysis and PPP. Due to the rapid proliferation of tumor cells and the intensified metabolic rate, tumor energy metabolism has become a target for disrupting the redox homeostasis and induce ferroptosis. Based on these emerging insights, regulatory impact of those‐tumor specific metabolic aberrations is systematically characterized, such as rewired glucose metabolism and metabolic compensation through glutamine utilization on ferroptosis and analyzed the underlying molecular mechanisms. Additionally, those ferroptosis‐based therapeutic strategies are also discussed by exploiting those metabolic vulnerabilities, which may open up new avenues for tumor treatment in a clinical context. Abstract : Ferroptosis is regulated by a variety of metabolic pathways, but the involvement of energy metabolism is rarely investigated. This review discusses the functional roles of various tumor metabolic phenotypes on ferroptosis regulation in the tumor landscape, which may improve the understanding of the tumor ferroptosis network and provide implications for the development of novel ferroptosis‐based therapies.