| Literature DB >> 28273483 |
Can E Senkal1, Mohamed F Salama2, Ashley J Snider3, Janet J Allopenna4, Nadia A Rana4, Antonius Koller5, Yusuf A Hannun1, Lina M Obeid6.
Abstract
In an approach aimed at defining interacting partners of ceramide synthases (CerSs), we found that fatty acyl-CoA synthase ACSL5 interacts with all CerSs. We demonstrate that ACSL5-generated FA-CoA was utilized with de novo ceramide for the generation of acylceramides, poorly studied ceramide metabolites. Functionally, inhibition of ceramide channeling to acylceramide enhanced accumulation of de novo ceramide and resulted in augmentation of ceramide-mediated apoptosis. Mechanistically, we show that acylceramide generation is catalyzed by diacylglycerol acyltransferase 2 (DGAT2) on lipid droplets. In summary, this study identifies a metabolic pathway of acylceramide generation and its sequestration in LDs in cells and in livers of mice on a high-fat diet. The study also implicates this pathway in ceramide-mediated apoptosis, and has implications in co-regulation of triglyceride and sphingolipid metabolisms. Published by Elsevier Inc.Entities:
Keywords: CerS; DGAT; acylceramide; apoptosis; ceramide; ceramide synthase; diacylglycerol acyltransferase; fatty acyl-CoA synthase; lipid droplets; sphingolipids
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Year: 2017 PMID： 28273483 PMCID： PMC5472424 DOI： 10.1016/j.cmet.2017.02.010
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287