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=Volume 3 - 2022

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=The human LIPA 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 Drosophila genome encodes for two LIPA orthologs, Magro and Lipase 3. We found previously that Lipase 3 transcription is highly induced in mutants with organelle defects. Here we show that Lipase 3 does neither hydrolyze triacylglycerol nor diacylglycerol. We generated a Lipase 3 mutant that accumulates phosphatidylinositol rather than storage lipids. We show that Lipase 3 is drastically upregulated in starved larvae and starved female flies, as well as in aged male flies. Lipase 3 mutants show sex-specific starvation resistance and a trend to lifespan extension. 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.