Emerging Roles of Ferroptosis in Human Diseases

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Cell Biology".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 32694

Special Issue Editors

Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea
Interests: ferroptosis; lipid metabolism; cancer metabolism; cardiovascular diseases; drug development
Special Issues, Collections and Topics in MDPI journals
School of Biosystems & Biomedical Sciences, College of Health Science, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
Interests: cancer metabolism; ferroptosis; entosis; non-apoptotic cell death; KRAS mutant cancers; YAP; nutrient transporters
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Ferroptosis, a recently recognized cell death modality dependent on iron and lipid peroxidation, is morphologically, biochemically, and genetically distinct from apoptosis, necroptosis, or other modes of cell death.

Increasing evidence indicates that ferroptosis has significant implications on various human diseases such as cancer, neurological and kidney diseases, and ischemia/reperfusion. The method of intervening in the occurrence or development of these diseases by regulating ferroptosis has attracted remarkable attention, and understanding the underlying mechanisms in ferroptosis will provide insight into the treatment of these intractable diseases.

This Special Issue, entitled “Emerging Roles of Ferroptosis in Human Diseases”, aims to present a collection of articles focused on the implications of ferroptosis on human diseases with an emphasis on recent developments in this field. Original research and review articles are welcome.

Dr. Eun-Woo Lee
Prof. Dr. Sung Eun Kim
Guest Editors

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Keywords

  • ferroptosis
  • regulated necrosis
  • non-apoptotic cell death
  • cancer
  • neurological disease
  • kidney disease
  • ischemia/reperfusion
  • iron metabolism
  • lipid peroxidation

Published Papers (5 papers)

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Research

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12 pages, 3978 KiB  
Article
A Novel Ferroptosis-Related Gene Signature Predicts Overall Survival of Breast Cancer Patients
by Haifeng Li, Lu Li, Cong Xue, Riqing Huang, Anqi Hu, Xin An and Yanxia Shi
Biology 2021, 10(2), 151; https://0-doi-org.brum.beds.ac.uk/10.3390/biology10020151 - 14 Feb 2021
Cited by 16 | Viewed by 4008
Abstract
Breast cancer is the second leading cause of death in women, thus a reliable prognostic model for overall survival (OS) in breast cancer is needed to improve treatment and care. Ferroptosis is an iron-dependent cell death. It is already known that siramesine and [...] Read more.
Breast cancer is the second leading cause of death in women, thus a reliable prognostic model for overall survival (OS) in breast cancer is needed to improve treatment and care. Ferroptosis is an iron-dependent cell death. It is already known that siramesine and lapatinib could induce ferroptosis in breast cancer cells, and some ferroptosis-related genes were closely related with the outcomes of treatments regarding breast cancer. The relationship between these genes and the prognosis of OS remains unclear. The data of gene expression and related clinical information was downloaded from public databases. Based on the TCGA-BRCA cohort, an 8-gene prediction model was established with the least absolute shrinkage and selection operator (LASSO) cox regression, and this model was validated in patients from the METABRIC cohort. Based on the median risk score obtained from the 8-gene model, patients were stratified into high- or low-risk groups. Cox regression analyses identified that the risk score was an independent predictor for OS. The findings from CIBERSORT and ssGSEA presented noticeable differences in enrichment scores for immune cells and pathways between the abovementioned two risk groups. To sum up, this prediction model has potential to be widely applied in future clinical settings. Full article
(This article belongs to the Special Issue Emerging Roles of Ferroptosis in Human Diseases)
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Review

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16 pages, 1487 KiB  
Review
Lipid Metabolism and Ferroptosis
by Ji-Yoon Lee, Won Kon Kim, Kwang-Hee Bae, Sang Chul Lee and Eun-Woo Lee
Biology 2021, 10(3), 184; https://0-doi-org.brum.beds.ac.uk/10.3390/biology10030184 - 02 Mar 2021
Cited by 123 | Viewed by 11763
Abstract
Ferroptosis is a type of iron-dependent regulated necrosis induced by lipid peroxidation that occurs in cellular membranes. Among the various lipids, polyunsaturated fatty acids (PUFAs) associated with several phospholipids, such as phosphatidylethanolamine (PE) and phosphatidylcholine (PC), are responsible for ferroptosis-inducing lipid peroxidation. Since [...] Read more.
Ferroptosis is a type of iron-dependent regulated necrosis induced by lipid peroxidation that occurs in cellular membranes. Among the various lipids, polyunsaturated fatty acids (PUFAs) associated with several phospholipids, such as phosphatidylethanolamine (PE) and phosphatidylcholine (PC), are responsible for ferroptosis-inducing lipid peroxidation. Since the de novo synthesis of PUFAs is strongly restricted in mammals, cells take up essential fatty acids from the blood and lymph to produce a variety of PUFAs via PUFA biosynthesis pathways. Free PUFAs can be incorporated into the cellular membrane by several enzymes, such as ACLS4 and LPCAT3, and undergo lipid peroxidation through enzymatic and non-enzymatic mechanisms. These pathways are tightly regulated by various metabolic and signaling pathways. In this review, we summarize our current knowledge of how various lipid metabolic pathways are associated with lipid peroxidation and ferroptosis. Our review will provide insight into treatment strategies for ferroptosis-related diseases. Full article
(This article belongs to the Special Issue Emerging Roles of Ferroptosis in Human Diseases)
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21 pages, 2025 KiB  
Review
Metabolic Regulation of Ferroptosis in Cancer
by Min Ji Kim, Greg Jiho Yun and Sung Eun Kim
Biology 2021, 10(2), 83; https://0-doi-org.brum.beds.ac.uk/10.3390/biology10020083 - 22 Jan 2021
Cited by 32 | Viewed by 6916
Abstract
Ferroptosis is a unique cell death mechanism that is executed by the excessive accumulation of lipid peroxidation in cells. The relevance of ferroptosis in multiple human diseases such as neurodegeneration, organ damage, and cancer is becoming increasingly evident. As ferroptosis is deeply intertwined [...] Read more.
Ferroptosis is a unique cell death mechanism that is executed by the excessive accumulation of lipid peroxidation in cells. The relevance of ferroptosis in multiple human diseases such as neurodegeneration, organ damage, and cancer is becoming increasingly evident. As ferroptosis is deeply intertwined with metabolic pathways such as iron, cyst(e)ine, glutathione, and lipid metabolism, a better understanding of how ferroptosis is regulated by these pathways will enable the precise utilization or prevention of ferroptosis for therapeutic uses. In this review, we present an update of the mechanisms underlying diverse metabolic pathways that can regulate ferroptosis in cancer. Full article
(This article belongs to the Special Issue Emerging Roles of Ferroptosis in Human Diseases)
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18 pages, 6558 KiB  
Review
Ferroptosis-Related Genes in Neurodevelopment and Central Nervous System
by Soo-Whee Kim, Yujin Kim, Sung Eun Kim and Joon-Yong An
Biology 2021, 10(1), 35; https://0-doi-org.brum.beds.ac.uk/10.3390/biology10010035 - 06 Jan 2021
Cited by 18 | Viewed by 4008
Abstract
Ferroptosis, first introduced as a new form of regulated cell death induced by erastin, is accompanied by the accumulation of iron and lipid peroxides, thus it can be inhibited either by iron chelators or by lipophilic antioxidants. In the past decade, multiple studies [...] Read more.
Ferroptosis, first introduced as a new form of regulated cell death induced by erastin, is accompanied by the accumulation of iron and lipid peroxides, thus it can be inhibited either by iron chelators or by lipophilic antioxidants. In the past decade, multiple studies have introduced the potential importance of ferroptosis in many human diseases, including cancer and neurodegenerative diseases. In this review, we will discuss the genetic association of ferroptosis with neurological disorders and development of the central nervous system. Full article
(This article belongs to the Special Issue Emerging Roles of Ferroptosis in Human Diseases)
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15 pages, 1415 KiB  
Review
The Intersection of DNA Damage Response and Ferroptosis—A Rationale for Combination Therapeutics
by Po-Han Chen, Watson Hua-Sheng Tseng and Jen-Tsan Chi
Biology 2020, 9(8), 187; https://0-doi-org.brum.beds.ac.uk/10.3390/biology9080187 - 23 Jul 2020
Cited by 23 | Viewed by 5132
Abstract
Ferroptosis is a novel form of iron-dependent cell death characterized by lipid peroxidation. While the importance and disease relevance of ferroptosis are gaining recognition, much remains unknown about its interaction with other biological processes and pathways. Recently, several studies have identified intricate and [...] Read more.
Ferroptosis is a novel form of iron-dependent cell death characterized by lipid peroxidation. While the importance and disease relevance of ferroptosis are gaining recognition, much remains unknown about its interaction with other biological processes and pathways. Recently, several studies have identified intricate and complicated interplay between ferroptosis, ionizing radiation (IR), ATM (ataxia–telangiectasia mutated)/ATR (ATM and Rad3-related), and tumor suppressor p53, which signifies the participation of the DNA damage response (DDR) in iron-related cell death. DDR is an evolutionarily conserved response triggered by various DNA insults to attenuate proliferation, enable DNA repairs, and dispose of cells with damaged DNA to maintain genome integrity. Deficiency in proper DDR in many genetic disorders or tumors also highlights the importance of this pathway. In this review, we will focus on the biological crosstalk between DDR and ferroptosis, which is mediated mostly via noncanonical mechanisms. For clinical applications, we also discuss the potential of combining ionizing radiation and ferroptosis-inducers for synergistic effects. At last, various ATM/ATR inhibitors under clinical development may protect ferroptosis and treat many ferroptosis-related diseases to prevent cell death, delay disease progression, and improve clinical outcomes. Full article
(This article belongs to the Special Issue Emerging Roles of Ferroptosis in Human Diseases)
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