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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2007.10.048 Byline: Deborah L. Berry (1)(2), Eric H. Baehrecke (1)(3) Keywords: CELLBIO; DEVBIO; SIGNALING Abstract: Autophagy is a catabolic process that is negatively regulated by growth and has been implicated in cell death. We find that autophagy is induced following growth arrest and precedes developmental autophagic cell death of Drosophila salivary glands. Maintaining growth by expression of either activated Ras or positive regulators of the class I phosphoinositide 3-kinase (PI3K) pathway inhibits autophagy and blocks salivary gland cell degradation. Developmental degradation of salivary glands is also inhibited in autophagy gene (atg) mutants. Caspases are active in PI3K-expressing and atg mutant salivary glands, and combined inhibition of both autophagy and caspases increases suppression of gland degradation. Further, induction of autophagy is sufficient to induce premature cell death in a caspase-independent manner. Our results provide in vivo evidence that growth arrest, autophagy, and atg genes are required for physiological autophagic cell death and that multiple degradation pathways cooperate in the efficient clearance of cells during development. Author Affiliation: (1) Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, MD 20742, USA (2) Present address: Children's National Medical Center, Washington, DC 20010, USA (3) Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA Article History: Received 12 June 2007; Revised 7 September 2007; Accepted 16 October 2007 Article Note: (miscellaneous) Published: December 13, 2007