A screen for yeast mutants revealed that a vacuolar complex containing the Gtr2 small GTPase and two new proteins, Ego1 and Ego3, were needed for exit from growth arrest. The complex seems to activate microautophagy—the formation and release of vesicles into the vacuolar lumen. This process counteracts macroautophagy-induced vacuole growth, which occurs upon TOR inhibition and growth arrest. In ego or gtr2 mutants, vacuoles thus continued to grow even under conditions that were expected to reactivate TOR.
This vacuolar growth would maintain a low concentration of amino acids, which the vacuole generates during protein degradation. But EGO-activated microautophagy, and the resulting shrunken vacuole, might increase vacuolar nutrient concentration enough to allow TOR reactivation and release cells from growth arrest when external nutrients are also sufficient. “It's a new way to look at the vacuole,” says De Virgilio, “as an intracellular nutrient pool that may affect cellular growth. Now we need to ask, what kind of signals does EGO respond to?” Genetic interactions suggest that glutamine is a good candidate, although the authors are also considering phospholipids.