AUTHOR=Hänschke Lea , Heier Christoph , Maya Palacios Santiago José , Özek Huseyin Erdem , Thiele Christoph , Bauer Reinhard , Kühnlein Ronald P. , Bülow Margret H. 

TITLE=Drosophila Lipase 3 Mediates the Metabolic Response to Starvation and Aging

JOURNAL=Frontiers in Aging

VOLUME=3

YEAR=2022

URL=https://www.frontiersin.org/journals/aging/articles/10.3389/fragi.2022.800153

DOI=10.3389/fragi.2022.800153

ISSN=2673-6217

ABSTRACT=<p>The human <italic>LIPA</italic> gene encodes for the enzyme lysosomal acid lipase, which hydrolyzes cholesteryl ester and triacylglycerol. Lysosomal acid lipase deficiency results in Wolman disease and cholesteryl ester storage disease. The <italic>Drosophila</italic> genome encodes for two LIPA orthologs, Magro and Lipase 3. Magro is a gut lipase that hydrolyzes triacylglycerides, while Lipase 3 lacks characterization based on mutant phenotypes. We found previously that <italic>Lipase 3</italic> transcription is highly induced in mutants with defects in peroxisome biogenesis, but the conditions that allow a similar induction in wildtypic flies are not known. Here we show that <italic>Lipase 3</italic> is drastically upregulated in starved larvae and starved female flies, as well as in aged male flies. We generated a lipase 3 mutant that shows sex-specific starvation resistance and a trend to lifespan extension. Using lipidomics, we demonstrate that Lipase 3 mutants accumulate phosphatidylinositol, but neither triacylglycerol nor diacylglycerol. Our study suggests that, in contrast to its mammalian homolog LIPA, Lipase 3 is a putative phospholipase that is upregulated under extreme conditions like prolonged nutrient deprivation and aging.</p>