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

Journal article


Forte, Gabriella M., Davie, Elizabeth, Lie, Shervi, Franz-Wachtel, Mirita, Ovens, Ashley J., Wang, Tingting, Oakhill, Jonathan S., Maček, Boris, Hagan, Iain M. and Petersen, Janni. (2019). Import of extracellular ATP in yeast and man modulates AMPK and TORC1 signalling. Journal of Cell Science. 132(7), pp. 1 - 15. https://doi.org/10.1242/jcs.223925
AuthorsForte, Gabriella M., Davie, Elizabeth, Lie, Shervi, Franz-Wachtel, Mirita, Ovens, Ashley J., Wang, Tingting, Oakhill, Jonathan S., Maček, Boris, Hagan, Iain M. and Petersen, Janni
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 (Schizosaccharomyces pombe) 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 cell growth.

KeywordsATP; AMP; TORC1; AMPK; Ssp2; Tsc1; Tsc2; schizosaccharomyces pombe; fission yeast; nutrient stress
Year2019
JournalJournal of Cell Science
Journal citation132 (7), pp. 1 - 15
PublisherThe Company of Biologists Ltd.
ISSN0021-9533
Digital Object Identifier (DOI)https://doi.org/10.1242/jcs.223925
Scopus EID2-s2.0-85064239994
Open accessOpen access
Page range1 - 15
Research GroupMary MacKillop Institute for Health Research
Publisher's version
License
Grant IDARC/DP180101682
Place of publicationUnited Kingdom
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