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Import of extracellular ATP in yeast and man modulates AMPK and TORC1 signalling
Forte, Gabriella M. Davie, Elizabeth Lie, Shervi Franz-Wachtel, Mirita Ovens, Ashley J. Wang, Tingting Oakhill, Jonathan S. Maček, Boris Hagan, Iain M. Petersen, Janni
Forte, Gabriella M.
Davie, Elizabeth
Lie, Shervi
Franz-Wachtel, Mirita
Ovens, Ashley J.
Wang, Tingting
Oakhill, Jonathan S.
Maček, Boris
Hagan, Iain M.
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.
Keywords
ATP, AMP, TORC1, AMPK, Ssp2, Tsc1, Tsc2, schizosaccharomyces pombe, fission yeast, nutrient stress
Date
2019
Type
Journal article
Journal
Journal of Cell Science
Book
Volume
132
Issue
7
Page Range
1-15
Article Number
ACU Department
Collections
Relation URI
Source URL
Event URL
Open Access Status
Open access
License
CC BY 4.0
File Access
Open