Sphingolipid Metabolism and Signaling

Mammalian cell-derived fatty acid biosynthesis derailment products are pro-inflammatory signalling molecules at the orphan receptor GPR84

This study identifies Cn-alkylpyrones as endogenous agonists for GPR84, linking fatty acid biosynthesis derailment to pro-inflammatory signaling through KR inhibition.

In vitro and in silico characterization of human PHOSPHO2 reveals its phospholipid phosphatase activity

This study characterizes PHOSPHO2 as a novel Mg2+-dependent, NEM-sensitive phosphatase with PAP activity toward multiple lipid substrates.

Impact of the sphingolipid metabolizing enzyme β-galactosylceramidase on mitochondrial sphingolipid profile and energetic metabolism in human melanoma cells

This study shows that knocking out β-galactosylceramidase in human melanoma cells reduces mitochondrial sphingolipids, leading to impaired energy metabolism and bioenergetic insufficiency.

KPB82 potently and selectively inhibits ACER2 and protects tumor and primary cells from doxorubicin-induced cytotoxicity

This paper identifies KPB82 as a potent and selective ACER2 inhibitor that reduces doxorubicin-induced cytotoxicity in multiple cell types.

Plasma Extracellular Vesicle Lipidomics Reveals an SMPD1-Driven Sphingomyelin Salvage Pathway Collapse in Parkinson's Disease

The paper identifies SMPD1-driven disruption of the ceramide-sphingomyelin axis in Parkinson's disease using plasma extracellular vesicle lipidomics and validates findings across multiple models.

ORMDL3-mediated SPT regulation Coordinates Myelin Sphingolipid and Protein Synthesis in Oligodendrocytes

This study shows that ORMDL3 regulates sphingolipid and protein synthesis in oligodendrocytes, affecting myelin structure and composition during development.

Glucosylceramide synthase is required for C6-ceramide nanoliposome-induced organelle stress and cell death

This study shows that glucosylceramide synthase inhibition protects cells from ceramide nanoliposome-induced death by preventing glycosphingolipid accumulation.

Acid Stress-induced plasma membrane ceramide arises from lysosome-plasma membrane fusion

The paper identifies a lysosome-to-plasma membrane pathway for stress-induced plasma membrane ceramide generation, showing lysosomal ceramide is transferred to the plasma membrane under acidic stress.

Fibrotic lung-derived sphingosine-1-phosphate drives emotion-like disorders by regulating hippocampal neuroinflammation and cell death

This study shows that S1P from fibrotic lungs causes neuroinflammation and mood disorders by acting on the hippocampus, and inhibiting S1P pathways can alleviate these effects.

Sphingolipid metabolism-related genes as key regulatory hubs in white smoke inhalation induced lung injury

This study identifies Top2a as a key regulatory hub in white smoke inhalation-induced lung injury and suggests thalidomide as a potential therapeutic candidate.

PERK/ATF3-dependent induction of GDE4 modulates intracellular lysophospholipid-PPARα/γ signaling

This study identifies GDE4 as a PERK/ATF3-induced lysophospholipase that modulates intracellular LPA levels and PPARα/γ signaling in prostate cancer cells under ER stress.

Sphingosine 1-phosphate receptor-1 signaling enhances neutrophil survival while suppressing inflammation and bacterial host defense functions

This study shows that S1PR1 signaling in neutrophils enhances their survival and reduces inflammation but impairs bacterial clearance and protects against lung injury in viral infections.

Targeting Tumor-derived Sphingosine Kinase 2 Unleashes Antitumor Immunity and Improves Survival of Mice with Group 3 Medulloblastoma

This study identifies SPHK2 as a therapeutic target in G3MB, showing that its inhibition restores anti-tumor immunity and improves survival in mouse models, with enhanced effects when combined with radiation.

Structure and mechanism of human sphingosine-1-phosphate transporter MFSD2B

This study determines the cryo-EM structure of MFSD2B bound to S1P and identifies its transport mechanism through mutagenesis and simulations.

Discovery of dihydroxy-enone-type protein-bound ceramides as the dominant type in human stratum corneum

The paper identifies dihydroxy-enone-type protein-bound ceramides as the dominant class in human stratum corneum, distinct from mouse epidermis.

Glycosylceramide assembly and function in a model bryophyte

This study investigates glycosylceramide assembly and function in the moss Physcomitrium patens by generating and analyzing mutants with defects in sphingolipid desaturation and glycosylceramide synthesis.

ALDH3A2 acts as a metabolic safeguard that regulates sphingolipid metabolism to suppress DNA damage and cell death

This study identifies ALDH3A2 as a metabolic safeguard that suppresses DNA damage and cell death by regulating hexadecenal metabolism during sphingolipid degradation.

Spatial MALDI-MSI Reveals a Coordinated Vicious Cycle of Oxidative Membrane Damage and Ceramide-Driven Sphingolipid Dysregulation in the Chronically Neuroinflamed Brain

This study uses MALDI-MSI to show that chronic neuroinflammation causes spatial lipidomic changes in rat brains, including oxidative stress and sphingolipid dysregulation, particularly in the hippocampus and white matter.

Neutral Sphingomyelinase-2 Restrains TAZ to Suppress Breast Tumor Growth

This study identifies nSMase2 as a metabolic tumor suppressor in breast cancer by restraining TAZ and inhibiting tumorigenesis.

Age-Dependent Spatiotemporal Remodeling of Brain Sphingolipids During LPS-Induced Neuroinflammation: MALDI-MSI Reveals Accelerated Sphingomyelin Depletion and Sulfatide Accumulation Linked to Mitochondrial Oxidative Stress

This study uses MALDI-MSI to show age-dependent sphingolipid changes in rat brains after LPS, linking sphingomyelin loss and sulfatide gain to mitochondrial stress.

Oncogene-driven metabolic regulation of Dihydroceramide Desaturase 1 (DES1) converges on GAPDH in matrix-detached conditions

This study identifies a novel pathway where oncogenic PI3K pathway drives DES1 activity through GAPDH in matrix-detached conditions, linking glucose and sphingolipid metabolism.

Comprehensive lipidomics of tissue macrophages reveal LTE4-driven eosinophil survival

The paper identifies GATA6's role in regulating sphingolipid and CysLT metabolism in peritoneal macrophages, leading to eosinophil survival via CysLT signaling.

Ceramide Synthases Regulate Myristate-Induced Intestinal IRE1α Activation

This study shows myristate induces ER stress via ceramide synthases, and restoring sphingoid bases reduces intestinal ER stress.

Monitoring Sphingomyelin Biosynthesis at Nanoscale Resolution by Expansion Microscopy

This paper develops a fluorometric assay combined with expansion microscopy to visualize sphingomyelin biosynthesis at nanoscale resolution in cells.

Sphingolipid regulation by yeast Mdm1 supports adaptive remodeling of the methionine transporter Mup1

This study shows that yeast Mdm1 links sphingolipid homeostasis to Mup1 endocytic remodeling, improving amino acid homeostasis and lifespan under nutrient limitation.

Lysophosphatidic Acid (LPA) Salivary Species Detection and Whole-mount LPA Receptor Localization in Mouse Salivary Gland

This study examines LPA levels and LPAR expression in mouse salivary glands during periodontal disease, finding increased LPA and specific LPAR subtypes.

Sphingosine-1-phosphate cross-talks to Notch via a S1PR1-Dll4-MPDZ complex to regulate endothelial barrier function

This study identifies a novel S1PR1-Dll4-MPDZ-Notch1 signaling pathway that enhances endothelial barrier integrity through Notch activation and Rac1 activity.

CYP4F2-mediated ω-hydroxylation of 1-deoxysphingolipids reveals a new hepatic detoxification pathway

This study identifies CYP4F2 as a key enzyme mediating ω-hydroxylation of 1-deoxySLs, revealing a new hepatic detoxification pathway that reduces their cytotoxicity.

Pyridoxine supplementation confers protection against SGPL1R222Q variant sphingosine phosphate lyase insufficiency syndrome

The paper shows pyridoxine supplementation improves SPLIS symptoms in a patient and mouse model by reducing S1P levels and enhancing SPL activity.

Uncoupling of nutrient sensing and cell size control by specific defects in ceramide structure

This study shows that specific ceramide structural features, particularly acyl chain length and sphingoid base hydroxylation, differentially regulate nutrient sensing, TORC2 signaling, and cell size control in yeast.