A combined proteomic and genetic analysis identifies a role for the lipid desaturase Desat1 in starvation-induced autophagy in Drosophila.
Autophagy is a lysosomal-mediated degradation process that promotes cell survival during nutrient-limiting conditions. However, excessive autophagy results in cell death. In Drosophila, autophagy is regulated nutritionally, hormonally and developmentally in several tissues, including the fat body, a nutrient-storage organ. Here we use a proteomics approach to identify components of starvation-induced autophagic responses in the Drosophila fat body. Using cICAT labeling and mass spectrometry, differences in protein expression levels of normal compared to starved fat bodies were determined. Candidates were analyzed genetically for their involvement in autophagy in fat bodies deficient for the respective genes. One of these genes, Desat1, encodes a lipid desaturase. Desat1 mutant cells fail to induce autophagy upon starvation. The desat1 protein localizes to autophagic structures after nutrient depletion and is required for fly development. Lipid analyses revealed that Desat1 regulates the composition of lipids in Drosophila. We propose that Desat1 exerts its role in autophagy by controlling lipid biosynthesis and/or signaling necessary for autophagic responses.
Köhler
Katja
K
Institute of Molecular Systems Biology, Swiss Federal Institute of Technology Zürich, Zürich, Switzerland.
Brunner
Erich
E
Guan
Xue Li
XL
Boucke
Karin
K
Greber
Urs F
UF
Mohanty
Sonali
S
Barth
Julia M I
JM
Wenk
Markus R
MR
Hafen
Ernst
E
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000201:enzymology* / Q000502:physiology*; D005216:Fat Body / Q000166:cytology / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D040901:Proteomics / Q000379:methods*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D029721:Drosophila Proteins; D011993:Recombinant Fusion Proteins; D044943:Fatty Acid Desaturases; C408225:desat1 protein, Drosophila