A novel function of sphingosine kinase 2 in the metabolism of sphinga-4,14-diene lipids

• DOI: 10.1101/2020.02.14.949974
• Publication Date: 2020-02-15T05:34:22Z
• Authors: Timothy A Couttas; Yepy H Rustam; Huitong Song; Yanfei Qi; Jonathan D Teo; Jinbiao Chen; Gavin E Reid; Anthony S Don
• Keywords: Sphingolipid; Sphingosine Kinase; Catabolism

Abstract The number, position, and configuration of double bonds in lipid acyl chains affects membrane packing, fluidity, recruitment signalling proteins. Studies on mammalian sphingolipids have focused those with a saturated sphinganine or mono-unsaturated sphingosine long chain base. Sphingolipids diunsaturated sphingadiene base been reported but are poorly characterised. Employing high-resolution untargeted mass spectrometry, we observed marked accumulation lipids containing base, not more common backbone, the hippocampus mice lacking metabolic enzyme kinase 2 (SphK2). Applying ultraviolet photodissociation tandem spectrometry (UVPD-MS/MS) were confidently assigned to C4-C5 C14-C15 positions sphingoid Sphingosine kinases involved lysosomal catabolism all sphingolipids, producing phosphates that irreversibly degraded by 1-phosphate lyase. Both SphK1 SphK2 phosphorylated sphinga-4,14-diene as efficiently sphingosine, however deuterated tracer experiments demonstrated ceramides rapidly metabolised cultured cells than silencing significantly impeded both sphingosine- sphingadiene-based sphingolipids. Since is dominant brain, propose SphK2-deficient brains results from intrinsically slower lipids, combined bottleneck catabolic pathway created absence SphK2. We speculate these function may affect fluidity properties cell membranes.