In Drosophila, the fat body undergoes a massive burst of autophagy at the end of larval development in preparation for the pupal transition. To identify genes involved in this process, we carried out a microarray analysis. We found that mRNA levels of the homologs of Atg8, the coat protein of early autophagic structures, and lysosomal hydrolases were upregulated, consistent with previous results. Genes encoding mitochondrial proteins and many chaperones were downregulated, including the inhibitor of eIF2alpha kinases and the peptidyl-prolyl cis-trans isomerase FK506-binding protein of 39kDa (FKBP39). Genetic manipulation of FKBP39 expression had a significant effect on autophagy, potentially through modulation of the transcription factor Foxo. Accordingly, we found that Foxo mutants cannot properly undergo autophagy in response to starvation, and that overexpression of Foxo induces autophagy.
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Acknowledgements. We thank Zsoltné Pálfia, Mariann Saródy and Emese Léder for the excellent technical assistance, our colleagues listed in the Materials and Methods section for providing reagents, and our anonymous reviewers for their helpful comments. This work was supported by NIH grant RO1 GM62509 provided to TPN and by the Hungarian Ministry of Education grant MEDICHEM 1/047 NKFP provided to MS.