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

AMP-activated kinase ( AMPK) and Target Of Rapamycin ( TOR) signallingcoordinate cell growth, proliferation, metabolism, and cell survival with the nutrient environment of cells. The poor vasculature and nutritional stress experienced by cells in solid tumoursraises 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 AMPKand 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 probenecidblocked ATP import into human cell linessuggesting 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 tumoursis both scavenged and recognized as an additional energy source beneficial for cells growth.