9
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Emerging significance and therapeutic targets of ferroptosis: a potential avenue for human kidney diseases

      review-article
      , , ,
      Cell Death & Disease
      Nature Publishing Group UK
      Natural products, Cell death, Kidney diseases

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Kidney diseases remain one of the leading causes of human death and have placed a heavy burden on the medical system. Regulated cell death contributes to the pathology of a plethora of renal diseases. Recently, with in-depth studies into kidney diseases and cell death, a new iron-dependent cell death modality, known as ferroptosis, has been identified and has attracted considerable attention among researchers in the pathogenesis of kidney diseases and therapeutics to treat them. The majority of studies suggest that ferroptosis plays an important role in the pathologies of multiple kidney diseases, such as acute kidney injury (AKI), chronic kidney disease, and renal cell carcinoma. In this review, we summarize recently identified regulatory molecular mechanisms of ferroptosis, discuss ferroptosis pathways and mechanisms of action in various kidney diseases, and describe the protective effect of ferroptosis inhibitors against kidney diseases, especially AKI. By summarizing the prominent roles of ferroptosis in different kidney diseases and the progress made in studying ferroptosis, we provide new directions and strategies for future research on kidney diseases. In summary, ferroptotic factors are potential targets for therapeutic intervention to alleviate different kidney diseases, and targeting them may lead to new treatments for patients with kidney diseases.

          Related collections

          Most cited references306

          • Record: found
          • Abstract: found
          • Article: not found

          Ferroptosis: an iron-dependent form of nonapoptotic cell death.

          Nonapoptotic forms of cell death may facilitate the selective elimination of some tumor cells or be activated in specific pathological states. The oncogenic RAS-selective lethal small molecule erastin triggers a unique iron-dependent form of nonapoptotic cell death that we term ferroptosis. Ferroptosis is dependent upon intracellular iron, but not other metals, and is morphologically, biochemically, and genetically distinct from apoptosis, necrosis, and autophagy. We identify the small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices, suggesting similarities between these two processes. Indeed, erastin, like glutamate, inhibits cystine uptake by the cystine/glutamate antiporter (system x(c)(-)), creating a void in the antioxidant defenses of the cell and ultimately leading to iron-dependent, oxidative death. Thus, activation of ferroptosis results in the nonapoptotic destruction of certain cancer cells, whereas inhibition of this process may protect organisms from neurodegeneration. Copyright © 2012 Elsevier Inc. All rights reserved.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Regulation of ferroptotic cancer cell death by GPX4.

            Ferroptosis is a form of nonapoptotic cell death for which key regulators remain unknown. We sought a common mediator for the lethality of 12 ferroptosis-inducing small molecules. We used targeted metabolomic profiling to discover that depletion of glutathione causes inactivation of glutathione peroxidases (GPXs) in response to one class of compounds and a chemoproteomics strategy to discover that GPX4 is directly inhibited by a second class of compounds. GPX4 overexpression and knockdown modulated the lethality of 12 ferroptosis inducers, but not of 11 compounds with other lethal mechanisms. In addition, two representative ferroptosis inducers prevented tumor growth in xenograft mouse tumor models. Sensitivity profiling in 177 cancer cell lines revealed that diffuse large B cell lymphomas and renal cell carcinomas are particularly susceptible to GPX4-regulated ferroptosis. Thus, GPX4 is an essential regulator of ferroptotic cancer cell death. Copyright © 2014 Elsevier Inc. All rights reserved.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Ferroptosis: mechanisms, biology and role in disease

              The research field of ferroptosis has seen exponential growth over the past few years, since the term was coined in 2012. This unique modality of cell death, driven by iron-dependent phospholipid peroxidation, is regulated by multiple cellular metabolic pathways, including redox homeostasis, iron handling, mitochondrial activity and metabolism of amino acids, lipids and sugars, in addition to various signalling pathways relevant to disease. Numerous organ injuries and degenerative pathologies are driven by ferroptosis. Intriguingly, therapy-resistant cancer cells, particularly those in the mesenchymal state and prone to metastasis, are exquisitely vulnerable to ferroptosis. As such, pharmacological modulation of ferroptosis, via both its induction and its inhibition, holds great potential for the treatment of drug-resistant cancers, ischaemic organ injuries and other degenerative diseases linked to extensive lipid peroxidation. In this Review, we provide a critical analysis of the current molecular mechanisms and regulatory networks of ferroptosis, the potential physiological functions of ferroptosis in tumour suppression and immune surveillance, and its pathological roles, together with a potential for therapeutic targeting. Importantly, as in all rapidly evolving research areas, challenges exist due to misconceptions and inappropriate experimental methods. This Review also aims to address these issues and to provide practical guidelines for enhancing reproducibility and reliability in studies of ferroptosis. Finally, we discuss important concepts and pressing questions that should be the focus of future ferroptosis research.
                Bookmark

                Author and article information

                Contributors
                fanyumei@hebtu.edu.cn
                tanke@hebtu.edu.cn
                Journal
                Cell Death Dis
                Cell Death Dis
                Cell Death & Disease
                Nature Publishing Group UK (London )
                2041-4889
                22 September 2023
                22 September 2023
                September 2023
                : 14
                : 9
                : 628
                Affiliations
                Ministry of Education Key Laboratory of Molecular and Cellular Biology; Hebei Research Center of the Basic Discipline of Cell Biology, Hebei Province Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology, College of Life Sciences, Hebei Normal University, ( https://ror.org/004rbbw49) Shijiazhuang, Hebei China
                Author information
                http://orcid.org/0000-0002-0781-6681
                Article
                6144
                10.1038/s41419-023-06144-w
                10516929
                37739961
                d4b7c9e9-7ddc-4ee4-862b-50b88ca65263
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 2 April 2023
                : 6 September 2023
                : 11 September 2023
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 31701006
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100002858, China Postdoctoral Science Foundation;
                Award ID: 2017M621099
                Award Recipient :
                Categories
                Review Article
                Custom metadata
                © Associazione Differenziamento e Morte Cellulare ADMC 2023

                Cell biology
                natural products,cell death,kidney diseases
                Cell biology
                natural products, cell death, kidney diseases

                Comments

                Comment on this article