A TORrific ATP sensor

Apositive regulator of growth called mTOR (mammalian Target of Rapamycin) is a direct detector of ATP levels, according to George Thomas (Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland) and colleagues. This connection from ATP to growth may explain why certain oxygen- and ATP-starved tumor cells are particularly sensitive to the mTOR- inhibitor rapamycin, as such tumors, through increased glycolysis and ATP production, may use the mTOR signaling pathway to proliferate.Dennis et al. began their studies with mTOR kinase assays. Results in several labs had been spotty, to the extent that mTOR's qualifications as a kinase were in question. “We were about ready to toss it out,” says Thomas.

But, by chance, the authors discovered that higher ATP concentrations converted mTOR into a robust kinase. Dropping ATP levels in vitro, or adding glycolytic inhibitors in vivo resulted in a...