Sphingosine-1-phosphate controls endothelial sphingolipid homeostasis via ORMDL

ABSTRACT: Disruption of sphingolipid homeostasis and signaling has been implicated in diabetes, cancer, cardiometabolic and neurodegenerative disorders. Yet, mechanisms governing cellular sensing and regulation of sphingolipid homeostasis remain largely unknown. In yeast, serine palmitoyltransferase, catalyzing the first and rate-limiting step of sphingolipid de novo biosynthesis, is negatively regulated by Orm1 and 2. Lowering sphingolipids triggers Orms phosphorylation, upregulation of serine palmitoyltransferase and sphingolipid de novo biosynthesis. However, mammalian orthologs ORMDLs lack the N-terminus hosting the phosphosites. Thus, which sphingolipid(s) are sensed by the cells, and mechanisms of homeostasis remain largely unknown. Here, we identify sphingosine-1-phosphate (S1P) as key sphin

SUBMITTER: Dr. Linda Sasset 

PROVIDER: S-SCDT-10_15252-EMBR_202254689 | biostudies-other |

REPOSITORIES: biostudies-other