88
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Mitochondrial metabolism and cancer

      review-article

      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

          Glycolysis has long been considered as the major metabolic process for energy production and anabolic growth in cancer cells. Although such a view has been instrumental for the development of powerful imaging tools that are still used in the clinics, it is now clear that mitochondria play a key role in oncogenesis. Besides exerting central bioenergetic functions, mitochondria provide indeed building blocks for tumor anabolism, control redox and calcium homeostasis, participate in transcriptional regulation, and govern cell death. Thus, mitochondria constitute promising targets for the development of novel anticancer agents. However, tumors arise, progress, and respond to therapy in the context of an intimate crosstalk with the host immune system, and many immunological functions rely on intact mitochondrial metabolism. Here, we review the cancer cell-intrinsic and cell-extrinsic mechanisms through which mitochondria influence all steps of oncogenesis, with a focus on the therapeutic potential of targeting mitochondrial metabolism for cancer therapy.

          Related collections

          Most cited references107

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

          On the origin of cancer cells.

          O WARBURG (1956)
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Senescent cells: an emerging target for diseases of ageing

            Chronological age represents the single greatest risk factor for human disease. One plausible explanation for this correlation is that mechanisms that drive ageing might also promote age-related diseases. Cellular senescence, which is a permanent state of cell cycle arrest induced by cellular stress, has recently emerged as a fundamental ageing mechanism that also contributes to diseases of late life, including cancer, atherosclerosis and osteoarthritis. Therapeutic strategies that safely interfere with the detrimental effects of cellular senescence, such as the selective elimination of senescent cells (SNCs) or the disruption of the SNC secretome, are gaining significant attention, with several programmes now nearing human clinical studies.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells.

              Interleukin-17 (IL-17)-secreting T cells of the T helper 17 (TH17) lineage play a pathogenic role in multiple inflammatory and autoimmune conditions and thus represent a highly attractive target for therapeutic intervention. We report that inhibition of acetyl-CoA carboxylase 1 (ACC1) restrains the formation of human and mouse TH17 cells and promotes the development of anti-inflammatory Foxp3(+) regulatory T (Treg) cells. We show that TH17 cells, but not Treg cells, depend on ACC1-mediated de novo fatty acid synthesis and the underlying glycolytic-lipogenic metabolic pathway for their development. Although TH17 cells use this pathway to produce phospholipids for cellular membranes, Treg cells readily take up exogenous fatty acids for this purpose. Notably, pharmacologic inhibition or T cell-specific deletion of ACC1 not only blocks de novo fatty acid synthesis but also interferes with the metabolic flux of glucose-derived carbon via glycolysis and the tricarboxylic acid cycle. In vivo, treatment with the ACC-specific inhibitor soraphen A or T cell-specific deletion of ACC1 in mice attenuates TH17 cell-mediated autoimmune disease. Our results indicate fundamental differences between TH17 cells and Treg cells regarding their dependency on ACC1-mediated de novo fatty acid synthesis, which might be exploited as a new strategy for metabolic immune modulation of TH17 cell-mediated inflammatory diseases.
                Bookmark

                Author and article information

                Journal
                Cell Res
                Cell Res
                Cell Research
                Nature Publishing Group
                1001-0602
                1748-7838
                March 2018
                08 December 2017
                1 March 2018
                : 28
                : 3
                : 265-280
                Affiliations
                [1 ]Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center , 10124 Torino, Italy
                [2 ]Department of Translational Medicine, University of Piemonte Orientale , 28100 Novara, Italy
                [3 ]Université Paris Descartes/Paris V, Sorbonne Paris Cité , 75006 Paris, France
                [4 ]Université Pierre et Marie Curie/Paris VI , 75006 Paris, France
                [5 ]Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers , 75006 Paris, France
                [6 ]INSERM, U1138 , 75006 Paris, France
                [7 ]Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , 94805 Villejuif, France
                [8 ]Pôle de Biologie, Hopitâl Européen George Pompidou, AP-HP , 75015 Paris, France
                [9 ]Department of Women's and Children's Health, Karolinska University Hospital , 17176 Stockholm, Sweden
                [10 ]Department of Radiation Oncology, Weill Cornell Medical College , New York, NY 10065, USA
                [11 ]Sandra and Edward Meyer Cancer Center , New York, NY 10065, USA
                Author notes
                [✝]

                These two authors contributed equally to this work.

                Article
                cr2017155
                10.1038/cr.2017.155
                5835768
                29219147
                9d70c89f-0a5c-4299-a5db-d0831b32510c
                Copyright © 2017 The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                Categories
                Review

                Cell biology
                autophagy,danger signaling,immunometabolism,oncometabolites,oxidative phosphorylation,mitophagy

                Comments

                Comment on this article