Phosphatidylinositol 5-phosphate 4-kinase (PIP4K) regulates sugar homeostasis in Drosophila

Metabolic adaptation such as sugar homeostasis is central to the response of living organisms to environmental changes and in insects, sugar homeostasis is an integral part of larval metabolism. Mutants of phosphatidylinositol 5-phosphate 4-kinase (dPIP4K) show altered growth and larval development. We find that dPIP4K mutants (dPIP4K29) show enhanced glucose uptake by the fat body, accompanied by increased circulating trehalose levels in feeding third instar larvae. Following acute starvation on a low sugar diet, dPIP4K29 larvae show reduced survival associated with high circulating trehalose levels, while under equivalent conditions, wild-type larvae undergo depletion of circulating trehalose. While Tret1-1PA transcripts were upregulated on starvation in muscle and brain tissue of controls, this enhancement was abrogated in dPIP4K29. Muscle specific depletion of Tret1-1PA in wild type larvae prevents reduction of circulating trehalose levels upon starvation, phenocopying that seen in dPIP4K29 and selective reconstitution of dPIP4K in muscle of dPIP4K29 could rescue starvation responses to wild type levels. Together, these findings identify dPIP4K as a key regulator of sugar homeostasis in larval tissues and survival in larvae during starvation.