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      Mitochondria on the move: Horizontal mitochondrial transfer in disease and health


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          Jiri Neuzil and colleagues review the processes and mechanisms that underlie horizontal mitochondrial transfer (HMT) and the metabolic consequences of HMT in cells.


          Mammalian genes were long thought to be constrained within somatic cells in most cell types. This concept was challenged recently when cellular organelles including mitochondria were shown to move between mammalian cells in culture via cytoplasmic bridges. Recent research in animals indicates transfer of mitochondria in cancer and during lung injury in vivo, with considerable functional consequences. Since these pioneering discoveries, many studies have confirmed horizontal mitochondrial transfer (HMT) in vivo, and its functional characteristics and consequences have been described. Additional support for this phenomenon has come from phylogenetic studies. Apparently, mitochondrial trafficking between cells occurs more frequently than previously thought and contributes to diverse processes including bioenergetic crosstalk and homeostasis, disease treatment and recovery, and development of resistance to cancer therapy. Here we highlight current knowledge of HMT between cells, focusing primarily on in vivo systems, and contend that this process is not only (patho)physiologically relevant, but also can be exploited for the design of novel therapeutic approaches.

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          Understanding the Warburg effect: the metabolic requirements of cell proliferation.

          In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed "the Warburg effect." Aerobic glycolysis is an inefficient way to generate adenosine 5'-triphosphate (ATP), however, and the advantage it confers to cancer cells has been unclear. Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer.
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            Biological properties of extracellular vesicles and their physiological functions

            In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.
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              Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis

              The use of extracellular vesicles, specifically exosomes, as carriers of biomarkers in extracellular spaces has been well demonstrated. Despite their promising potential, the use of exosomes in the clinical setting is restricted due to the lack of standardization in exosome isolation and analysis methods. The purpose of this review is to not only introduce the different types of extracellular vesicles but also to summarize their differences and similarities, and discuss different methods of exosome isolation and analysis currently used. A thorough understanding of the isolation and analysis methods currently being used could lead to some standardization in the field of exosomal research, allowing the use of exosomes in the clinical setting to become a reality.

                Author and article information

                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: VisualizationRole: Writing - original draftRole: Writing - review & editing
                Role: Writing - original draftRole: Writing - review & editing
                Role: InvestigationRole: Writing - original draft
                Role: VisualizationRole: Writing - original draftRole: Writing - review & editing
                Role: Writing - original draftRole: Writing - review & editing
                Role: ConceptualizationRole: Writing - original draftRole: Writing - review & editing
                Role: ConceptualizationRole: Data curationRole: SupervisionRole: Writing - original draftRole: Writing - review & editing
                J Cell Biol
                J Cell Biol
                The Journal of Cell Biology
                Rockefeller University Press
                06 March 2023
                16 February 2023
                16 February 2023
                : 222
                : 3
                : e202211044
                [1 ]School of Pharmacy and Medical Sciences, Griffith University ( https://ror.org/02sc3r913) , Southport, Australia
                [2 ]Institute of Biotechnology, Academy of Sciences of the Czech Republic ( https://ror.org/00wzqmx94) , Prague-West, Czech Republic
                [3 ]School of Medicine, University of Paris-East; , Creteil, France
                [4 ]Malaghan Institute of Medical Research; , Wellington, New Zealand
                [5 ]Faculty of Science, Charles University; , Prague, Czech Republic
                [6 ]First Faculty of Medicine, Charles University; , Prague, Czech Republic
                Author notes

                Disclosures: The authors declare no competing interests exist.

                Author information
                © 2023 Dong et al.

                This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).

                : 12 November 2022
                : 12 January 2023
                : 01 February 2023
                Funded by: Australian Research Council, DOI http://dx.doi.org/10.13039/501100000923;
                Funded by: Czech Science Foundation, DOI http://dx.doi.org/10.13039/501100001824;
                Award ID: 20-05942S
                Award ID: 21-04607X
                Award ID: 22-34507S
                Award ID: NU-22-34507S
                Funded by: Czech Health Foundation;
                Award ID: NU22-08-00160
                Funded by: Health Research Council of New Zealand, DOI http://dx.doi.org/10.13039/501100001505;
                Funded by: Cancer Society of New Zealand, DOI http://dx.doi.org/10.13039/501100001513;
                Cell Signaling
                Cell Metabolism

                Cell biology
                Cell biology


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