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

Area of Science:

• Cell Biology
• Metabolic Signaling
• Cancer Biology

Background:

• AMP-activated kinase (AMPK) and target of rapamycin (TOR) signaling pathways regulate cellular processes in response to nutrient availability.
• Solid tumors often face poor vasculature and nutritional stress, posing a challenge for cell survival and growth.

Purpose of the Study:

• To investigate how cells, particularly in nutrient-poor environments like solid tumors, assimilate nutrients to regulate AMPK and TOR signaling.
• To determine the role of extracellular ATP and AMP in cellular energy sensing and signaling pathways.

Main Methods:

• Experiments were conducted using human cell lines and fission yeast (Schizosaccharomyces pombe).
• Cells were exposed to varying concentrations of external ATP and AMP.
• The impact of these nucleotides on cell growth, AMPK, and TOR signaling was assessed.
• The role of the PANX1 channel in ATP import was investigated using probenecid, a PANX1 inhibitor.

Main Results:

• External AMP impeded cell growth in both yeast and human cells, with this effect requiring AMPK in yeast.
• External ATP rescued growth defects in yeast mutants with reduced TORC1 signaling.
• Exogenous ATP enhanced TORC1 signaling in both yeast and human cell lines.
• Probenecid blocked ATP import into human cells, suggesting PANX1's involvement in ATP transport.

Conclusions:

• Human and fission yeast cells can import external ATP and AMP to modulate AMPK and TOR signaling.
• Extracellular ATP may serve as an additional energy source for cells, particularly in the context of solid tumors.
• The PANX1 channel is implicated in the import and release of ATP in mammalian cells, highlighting its potential role in nutrient scavenging and signaling in tumors.