11
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Ferroptosis-related exosomal non-coding RNAs: promising targets in pathogenesis and treatment of non-malignant diseases

      review-article

      Read this article at

          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

          Ferroptosis, an iron-dependent form of programmed cell death, introduces a novel perspective on cellular demise. This study investigates the regulatory network of exosomal non-coding RNAs (ncRNAs), including miRNAs, circRNAs, and lncRNAs, in ferroptosis modulation. The primary goal is to examine the pathological roles of ferroptosis-related exosomal ncRNAs, particularly in ischemic reperfusion injuries. The research reveals intricate molecular interactions governing the regulatory interplay between exosomal ncRNAs and ferroptosis, elucidating their diverse roles in different non-malignant pathological contexts. Attention is given to their impact on diseases, including cardiac, cerebral, liver, and kidney ischemic injuries, as well as lung, wound, and neuronal injuries. Beyond theoretical exploration, the study provides insights into potential therapeutic applications, emphasizing the significance of mesenchymal stem cells (MSCs)-derived exosomes. Findings underscore the pivotal role of MSC-derived exosomal ncRNAs in modulating cellular responses related to ferroptosis regulation, introducing a cutting-edge dimension. This recognition emphasizes the importance of MSC-derived exosomes as crucial mediators with broad therapeutic implications. Insights unveil promising avenues for targeted interventions, capitalizing on the diverse roles of exosomal ncRNAs, providing a comprehensive foundation for future therapeutic strategies.

          Related collections

          Most cited references94

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

          The biology, function, and biomedical applications of exosomes

          The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Exosomes, with an average diameter of ~100 nanometers, are a subset of EVs. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate the final content of the exosomes. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. In various diseases, exosomes offer a window into altered cellular or tissue states, and their detection in biological fluids potentially offers a multicomponent diagnostic readout. The efficient exchange of cellular components through exosomes can inform their applied use in designing exosome-based therapeutics.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The CoQ oxidoreductase FSP1 acts in parallel to GPX4 to inhibit ferroptosis

            Ferroptosis is a form of regulated cell death that is caused by the iron-dependent peroxidation of lipids 1,2 . The glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4) prevents ferroptosis by converting lipid hydroperoxides into non-toxic lipid alcohols 3,4 . Ferroptosis has been implicated in the cell death that underlies several degenerative conditions 2 , and induction of ferroptosis by inhibition of GPX4 has emerged as a therapeutic strategy to trigger cancer cell death 5 . However, sensitivity to GPX4 inhibitors varies greatly across cancer cell lines 6 , suggesting that additional factors govern resistance to ferroptosis. Here, employing a synthetic lethal CRISPR/Cas9 screen, we identify ferroptosis suppressor protein 1 (FSP1) (previously known as apoptosis-inducing factor mitochondrial 2 (AIFM2)) as a potent ferroptosis resistance factor. Our data indicate that myristoylation recruits FSP1 to the plasma membrane where it functions as an oxidoreductase that reduces coenzyme Q10 (CoQ), generating a lipophilic radical-trapping antioxidant (RTA) that halts the propagation of lipid peroxides. We further find that FSP1 expression positively correlates with ferroptosis resistance across hundreds of cancer cell lines, and that FSP1 mediates resistance to ferroptosis in lung cancer cells in culture and in mouse tumor xenografts. Thus, our data identify FSP1 as a key component of a non-mitochondrial CoQ antioxidant system that acts in parallel to the canonical glutathione-based GPX4 pathway. These findings define a new ferroptosis suppression pathway and indicate that pharmacological inhibition of FSP1 may provide an effective strategy to sensitize cancer cells to ferroptosis-inducing chemotherapeutics.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Exosomes: biogenesis, biologic function and clinical potential

              Exosomes are nano-sized biovesicles released into surrounding body fluids upon fusion of multivesicular bodies and the plasma membrane. They were shown to carry cell-specific cargos of proteins, lipids, and genetic materials, and can be selectively taken up by neighboring or distant cells far from their release, reprogramming the recipient cells upon their bioactive compounds. Therefore, the regulated formation of exosomes, specific makeup of their cargo, cell-targeting specificity are of immense biological interest considering extremely high potential of exosomes as non-invasive diagnostic biomarkers, as well as therapeutic nanocarriers. In present review, we outline and discuss recent progress in the elucidation of the regulatory mechanisms of exosome biogenesis, the molecular composition of exosomes, and technologies used in exosome research. Furthermore, we focus on the potential use of exosomes as valuable diagnostic and prognostic biomarkers for their cell-lineage and state-specific contents, and possibilities as therapeutic vehicles for drug and gene delivery. Exosome research is now in its infancy, in-depth understanding of subcellular components and mechanisms involved in exosome formation and specific cell-targeting will bring light on their physiological activities.
                Bookmark

                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2614872/overviewRole: Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2587001/overviewRole: Role: Role: Role: Role:
                Journal
                Front Cell Dev Biol
                Front Cell Dev Biol
                Front. Cell Dev. Biol.
                Frontiers in Cell and Developmental Biology
                Frontiers Media S.A.
                2296-634X
                07 February 2024
                2024
                : 12
                : 1344060
                Affiliations
                [1] 1 School of Life Science , Fudan University , Shanghai, China
                [2] 2 Wanchuanhui (Shanghai) Medical Technology Co., Ltd. , Shanghai, China
                Author notes

                Edited by: Guangyong Peng, Washington University in St. Louis, United States

                Reviewed by: Menderes Yusuf Terzi, Mustafa Kemal University, Türkiye

                Chuanlin Ding, University of Louisville, United States

                *Correspondence: Jun Xie, xiejun@ 123456fudan.edu.cn
                [ † ]

                ORCID: Yiping Zhang, orcid.org/0009-0002-2329-8906; Jun Xie, orcid.org/0000-0003-4019-9248

                Article
                1344060
                10.3389/fcell.2024.1344060
                10879574
                38385027
                5a0fc2a8-e8d7-4bd4-8f75-523ecda7a7fd
                Copyright © 2024 Zhang and Xie.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 24 November 2023
                : 10 January 2024
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (30470356, 30300059), Fudan Medical Cell Rehabilitation School Enterprise Joint Research Center Fund (2020351), Key Projects of National Natural Science Foundation of China (32130044) and National Key R&D Plan (2017YFC0107600/04).
                Categories
                Cell and Developmental Biology
                Review
                Custom metadata
                Cell Death and Survival

                non-coding rnas,exosomes,ferroptosis,ischemic/reperfusion injury,organ injury

                Comments

                Comment on this article