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    Import of extracellular ATP in yeast and man modulates AMPK and TORC1 signalling

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    Authors
    Forte, GM
    Davie, E
    Lie, S
    Franz-Wachtel, M
    Ovens, AJ
    Wang, T
    Oakhill, JS
    Macek, B
    Hagan, Iain M
    Petersen, J
    Affiliation
    Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, M13 9PT, UK
    Issue Date
    2019
    
    Metadata
    Show full item record
    Abstract
    AMP-activated kinase (AMPK) and Target Of Rapamycin (TOR) signalling coordinate cell growth, proliferation, metabolism, and cell survival with the nutrient environment of cells. The poor vasculature and nutritional stress experienced by cells in solid tumours raises the question: how do they assimilate sufficient nutrients to survive? Here, we show that human and fission yeast cells import ATP and AMP from their external environment to regulate AMPK and TOR signalling. Exposure of fission yeast and human cells to external AMP impeded cell growth, however, in yeast this restraining impact required AMPK. In contrast, external ATP rescued the growth defect of yeast mutants with reduced TORC1 signalling, furthermore, exogenous ATP transiently enhanced TORC1 signalling in both yeast and human cell lines. Addition of the PANX1 channel inhibitor probenecid blocked ATP import into human cell lines suggesting that this channel may be responsible for both ATP release and uptake in mammals. In light of these findings it is possible that the higher extracellular ATP concentration reported in solid tumours is both scavenged and recognized as an additional energy source beneficial for cells growth.
    Citation
    Forte GM, Davie E, Lie S, Franz-Wachtel M, Ovens AJ, Wang T, et al. Import of extracellular ATP in yeast and man modulates AMPK and TORC1 signalling. J Cell Sci. 2019 Feb 27.
    Journal
    Journal of Cell Science
    URI
    http://hdl.handle.net/10541/621637
    DOI
    10.1242/jcs.223925
    PubMed ID
    30814334
    Additional Links
    https://dx.doi.org/10.1242/jcs.223925
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1242/jcs.223925
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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