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Microautophagy (arrows) is blocked without EGO2 (bottom). DE VIRGILIO/ELSEVIER

Nutrient starvation arrests cell growth by shutting down the insulin-sensitive TOR pathway. How cells get back into proliferation is largely unknown, despite the fact that escape from quiescence is a hallmark of cancer. Now, Frederique Dubouloz, Claudio De Virgilio, and colleagues (University of Geneva, Switzerland) suggest that nutrient sensing from the vacuolar membrane might control the return to proliferation.

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.

Reference:

Dubouloz, F., et al. 2005. Mol. Cell. 19:15–26.[CrossRef][Medline]

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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This Article PDF (Full Text) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Social Bookmarking                      What's this?