Unraveling the role of the Target of Rapamycin signaling in sphingolipid metabolism

Article ID	Journal	Published Year	Pages	File Type
8358936	Progress in Lipid Research	2016	25 Pages	PDF

Abstract

Sphingolipid metabolism and their route of synthesis are highly conserved from yeast to mammalian cells. Studies using the budding yeast Saccharomyces cerevisiae have served in many ways to foster our understanding of sphingolipid dynamics and their role in the regulation of cellular processes. In the past decade, studies in S. cerevisiae have unraveled a functional association between the Target of Rapamycin (TOR) pathway and sphingolipids, showing that both TOR Complex 1 (TORC1) and TOR Complex 2 (TORC2) branches control temporal and spatial aspects of sphingolipid metabolism in response to physiological and environmental cues. In this review, we report recent findings in this emerging and exciting link between the TOR pathway and sphingolipids and implications in human health and disease.

Keywords

ABC AMPK PI3K COX ABA Jnk SPH TOR GTP CMA ERK PP2A PDS DHS eIF2 pKa SPT IGF-1 FKBP12 PLC UPR ATG PKC IPC S1P CLS NCR NPC SMase c-Jun NH2-terminal kinase PDGF S1PR PAK1 PHS 4E-BP1 CK2 LC3B microtubule-associated protein 1 light chain 3B RTG GEF PDK1 PP1 CerS CWI TFEB LCB phytosphingosine eukaryotic translation initiation factor 4E binding protein 1 PIP2 dihydrosphingosine S6K TORC1 TORC2 FAPP C1P inositolphosphorylceramide RNA pol aureobasidin A MIPC M(IP)2C AMP-activated protein kinase Chaperone-mediated autophagy MAPK p21-activated kinase 1 ROS S6 kinase SGK Adenosine Triphosphate ATP RNA polymerase Sphingosine kinase Sphingosine-1-phosphate sphingosine sphingomyelinase Ultraviolet insulin-like growth factor-1 tumor necrosis factor α Hog Heat Temperature sensitive Ribosome biogenesis Ceramide-1-phosphate ceramide synthase cytochrome c oxidase endoplasmic reticulum Chronological lifespan Transcription factor EB retrograde Guanine exchange factor platelet-derived growth factor TNF-α Phosphatidylinositol 3-kinase phospholipase C autophagy-related Hydrophobic motif Niemann-Pick type C target of rapamycin Pleckstrin Homology Unfolded protein response FK506-binding protein protein phosphatase 1 protein phosphatase 2A protein kinase A Protein kinase C mitogen-activated protein kinase Serine palmitoyltransferase casein kinase II ATP-binding cassette Extracellular signal–regulated kinase high osmolarity glycerol Guanosine triphosphate Reactive oxygen species sphingosine-1-phosphate receptor cell wall integrity