Molecular mechanisms of metabolic reprogramming in proliferating cells: implications for T-cell-mediated immunity

Authors

  • Federica M. Marelli-Berg,

    1. William Harvey Research Institute – Heart Centre, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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  • Hongmei Fu,

    1. William Harvey Research Institute – Heart Centre, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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  • Claudio Mauro

    1. William Harvey Research Institute – Heart Centre, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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Dr C. Mauro, William Harvey Research Institute – Heart Centre, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Email: c.mauro@qmul.ac.uk
Senior author: Claudio Mauro

Summary

To engage in proliferation, cells need to increase their biomass and replicate their genome. This process presents a substantial bioenergetic challenge: proliferating cells must increase ATP production and acquire or synthesize raw materials, including lipids, proteins and nucleic acids. To do so, proliferating cells actively reprogramme their intracellular metabolism from catabolic mitochondrial oxidative phosphorylation (OXPHOS) to glycolysis and other anabolic pathways. This metabolic reprogramming, which directs nutrient uptake and metabolism during cell activation and proliferation, is under the control of specific signal transduction pathways. The underlying molecular mechanisms of cell metabolism reprogramming and their relevance to physiology and disease are currently under intense study. Several reports have uncovered the mechanisms of metabolic reprogramming that drive high rates of cell proliferation in cancer. Some recent studies have elucidated the physiological role of metabolic reprogramming during T-cell activation, differentiation and trafficking, which are potentially relevant to inflammatory disorders. This review describes the impact of metabolic reprogramming on the pathogenesis of cancer and the physiology of T-cell-mediated immune responses, with an emphasis on the phosphatidyl inositol 3-kinase–serine/threonine kinase–mammalian target of rapamycin pathway and the recently discovered metabolic processes regulated by nuclear factor-κB. These discoveries will hopefully translate into a better understanding of the role of metabolic reprogramming as a key regulator of T-cell-mediated immune responses and offer novel, immune-based therapeutic approaches.

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