The alpha/beta-hydrolase domain-containing 4-and 5-related phospholipase Pummelig controls energy storage in Drosophila[S]

Triglycerides (TGs) are the main energy storage form to accommodate for changing organismal energy demands. In Drosophila melanogaster, the TG lipase Brummer (Bmm; also known as DmATGL) is of central importance for body fat mobilization. The mammalian orthologue adipose triglyceride lipase (ATGL) becomes activated by the α/β-hydrolase fold domain containing 5 (ABHD5; also called CGI-58), one member of the paralogous gene pair ABHD4 and ABHD5. In Drosophila, the pummelig (puml) gene encodes the single sequence-related protein to mammalian ABHD4/ABHD5 with unknown function. Here we generate puml mutant flies, that are short-lived, store excess body fat on the expense of glycogen, and exhibit ectopic fat storage with altered TG fatty acid profile in the fly kidneys, called Malpighian tubules. TG accumulation in puml mutants is not associated with increased food intake but with elevated lipogenesis, while starvation-induced lipid mobilization is functional. Despite its structural similarity to mammalian ABHD5/CGI-58, Puml does not stimulate TG lipase activity of Bmm/DmATGL in vitro. However, a substrate screen identifies Puml as a phospholipase, that is localized on lipid droplets, mitochondria, and peroxisomes. In conclusion, our study identifies the ABHD4/5 family member Puml as a versatile phospholipase, which regulates Drosophila body fat storage and energy metabolism