Programmed autophagy in the Drosophila fat body is induced by ecdysone through regulation of the PI3K pathway.
Eukaryotic cells catabolize their own cytoplasm by autophagy in response to amino acid starvation and inductive signals during programmed tissue remodeling and cell death. The Tor and PI3K signaling pathways have been shown to negatively control autophagy in eukaryotes, but the mechanisms that link these effectors to overall animal development and nutritional status in multicellular organisms remain poorly understood. Here, we reveal a complex regulation of programmed and starvation-induced autophagy in the Drosophila fat body. Gain-of-function genetic analysis indicated that ecdysone receptor signaling induces programmed autophagy whereas PI3K signaling represses programmed autophagy. Genetic interaction studies showed that ecdysone signaling downregulates PI3K signaling and that this represents the effector mechanism for induction of programmed autophagy. Hence, these studies link hormonal induction of autophagy to the regulatory function of the PI3K signaling pathway in vivo.
Rusten
Tor Erik
TE
Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N-0310 Oslo.
Lindmo
Karine
K
Juhász
Gábor
G
Sass
Miklós
M
Seglen
Per O
PO
Brech
Andreas
A
Stenmark
Harald
H
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001343:Autophagy; D001921:Brain / Q000378:metabolism; D015536:Down-Regulation; D004330:Drosophila / Q000196:embryology* / Q000502:physiology*; D004440:Ecdysone / Q000378:metabolism*; D005216:Fat Body / Q000502:physiology*; D005508:Food Deprivation; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D049452:Green Fluorescent Proteins; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008164:Luminescent Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D013997:Time Factors
D000596:Amino Acids; D007166:Immunosuppressive Agents; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D004440:Ecdysone; D019869:Phosphatidylinositol 3-Kinases; D020123:Sirolimus