Abstract
Hunger drives food-seeking behaviour and controls adaptation of organisms to nutrient availability and energy stores. Lipids constitute an essential source of energy in the cell that can be mobilised during fasting by autophagy. Selective degradation of proteins by autophagy is made possible essentially by the presence of LIR and KFERQ-like motifs. Using in silico screening of Drosophila proteins that contain KFERQ-like motifs, we identified and characterized the adaptor protein Arouser, which functions to regulate fat storage and mobilisation and is essential during periods of food deprivation. We show that hypomorphic arouser mutants are not satiated, are more sensitive to food deprivation, and are more aggressive, suggesting an essential role for Arouser in the coordination of metabolism and food-related behaviour. Our analysis shows that Arouser functions in the fat body through nutrient-related signalling pathways and is degraded by endosomal microautophagy. Arouser degradation occurs during feeding conditions, whereas its stabilisation during non-feeding periods is essential for resistance to starvation and survival. In summary, our data describe a novel role for endosomal microautophagy in energy homeostasis, by the degradation of the signalling regulatory protein Arouser.
Highlights
The coordination of metabolism and feeding behaviour according to nutrient availability is crucial to maintain organismal homeostasis, fitness and survival
There are many different protein classes for each motif and, each class has a relatively low percentage of gene hits (
We identified Arouser as a novel endosomal microautophagy substrate, and we provide evidence that suggest its involvement in the regulation of lipid metabolism in the fat body
Summary
The coordination of metabolism and feeding behaviour according to nutrient availability is crucial to maintain organismal homeostasis, fitness and survival. In many animals during feeding excess nutrients such as carbohydrates are converted into lipids, mainly in the form triacylglycerols (TAGs), through a process called lipogenesis. The TAGs are stored as lipid droplets in adipose tissue. In Drosophila, the main adipose tissue is called the fat body (Rajan & Perrimon, 2013). The balance between lipogenesis and lipolysis is regulated by the nutrient sensing pathways of the mTOR complex (Cai et al, 2016). Insulin signalling is well established in regulating lipid metabolism and is well-conserved in all animals, including Drosophila (Saltiel & Kahn, 2001; Garofalo, 2002; Kannan & Fridell, 2013). Activation of mTOR due to overfeeding causes a severe downregulation of autophagy, leading to insulin resistance. Insulin-mediated mTOR signalling controls both autophagy and lysosome functions (Puertollano, 2014)
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