Sphingolipid Metabolism and Signaling

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.

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.

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.

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.

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.

Structural Mechanisms Underlying Distinct Binding and Activities of 18:0 and 18:1 Lysophosphatidic acids at LPA1 Receptor

This study investigates how 18:0 and 18:1 lysophosphatidic acids bind and activate LPA1 receptor differently using molecular dynamics simulations.

CerS2 is a druggable target in triple-negative breast cancer

This paper identifies DH20931 as a first-in-class agonist of CerS2 that induces ER stress and apoptosis in TNBC cells, showing preclinical efficacy.

ER-Localized Ceramide Accumulation Contributes to Replicative Senescence

This study identifies ER-localized ceramide accumulation as a driver of replicative senescence through impaired ceramide trafficking.

The Sphingosine-1-phosphate pathway is differentially activated in human gestational tissues.

This study profiles S1P metabolic enzymes and receptors in human gestational tissues across pregnancy, finding tissue-specific expression and abundance patterns.

Antidepressants interact with an LPA3 receptor binding site: functional and docking studies

This study investigates how antidepressants interact with LPA3 receptors through functional assays and docking simulations, revealing distinct effects on calcium and ERK 1/2 signaling.

Loss of sphingomyelin synthase-1 does not cause egg retention or locomotion defects in Caenorhabditis elegans

The paper investigates the role of sphingomyelin synthase-1 in C. elegans and finds that its loss does not cause egg retention or locomotion defects, suggesting potential background mutations in the studied mutant.

Sphingosine kinase 2 suppresses neutrophil responses to promote viral persistence while attenuating immune pathology

This study shows that SphK2 deficiency in neutrophils reduces immune suppression, enhances T cell responses, and decreases viral persistence during LCMV infection.

Inhibition of Acid Sphingomyelinase Links Sphingolipid Remodeling to Necroptotic Cell Death

This study identifies acid sphingomyelinase (ASMase) as a key regulator of ceramide levels during necroptosis, showing that its inhibition reduces membrane permeability by impairing MLKL pore formation.

1-Deoxysphingolipids dysregulate membrane properties and cargo trafficking in the early secretory pathway

This study investigates how 1-deoxysphingolipids affect membrane properties and cargo trafficking in the early secretory pathway by analyzing their subcellular distribution and effects on ER membrane fluidity and ERES.

Cholesterol depletion activates trafficking-coupled sphingolipid synthesis

The paper shows that cholesterol depletion increases VLC sphingomyelin synthesis by enhancing ER-to-Golgi trafficking of VLC-ceramide.

Mac/Lac-tosylceramide regulates intestinal homeostasis and secretory cell fate commitment by facilitating Notch signaling

This study identifies a specific glycosphingolipid metabolite that modulates Notch signaling in intestinal stem cells, affecting cell fate and tumor formation in both Drosophila and mammals.

Complex sphingolipids are essential for cell division and plasmodesmal development in the moss Physcomitrium patens

This study identifies the role of complex sphingolipids in cell division and plasmodesmal development in the moss Physcomitrium patens through mutant analysis.

Resolving vs. Non-resolving Sphingolipid Dynamics During Macrophage Activation: A Time-resolved Metabolic Analysis

This study maps sphingolipid dynamics in macrophages during inflammation, identifying resolving and non-resolving metabolites and suggesting targeted therapeutic strategies.

Loss of dihydroceramide desaturase drives neurodegeneration by disrupting endoplasmic reticulum and lipid droplet homeostasis in glial cells

This study shows that loss of dihydroceramide desaturase in glial cells causes neurodegeneration by disrupting ER and lipid droplet homeostasis, leading to neuronal death and developmental defects.

Glucose-dependent glycosphingolipid biosynthesis fuels CD8+ T cell function and tumor control

This study identifies glucose-dependent glycosphingolipid biosynthesis as essential for CD8+ T cell expansion and tumor control, independent of energy production.

CpgD is a phosphoglycerate cytidylyltransferase required for ceramide diphosphoglycerate synthesis

The paper identifies CpgD as a phosphoglycerate cytidylyltransferase essential for ceramide diphosphoglycerate synthesis in Caulobacter crescentus.

Multiple LPA3 receptor agonist binding sites evidenced under docking and functional studies

The paper identifies two distinct agonist binding cavities in the LPA3 receptor through docking and functional studies, showing differential ligand interactions and mutation sensitivity.

Bioinformatics analysis identifies sequence determinants of enzymatic activity for the PHARC associated lipase ABHD12

The paper identifies sequence determinants of ABHD12 enzymatic activity through bioinformatics and biochemical validation, and identifies a Drosophila ortholog with lyso-PS lipase activity.

The individual isoforms of ORMDL, the regulatory subunit of serine palmitoyltransferase, have distinctive sensitivities to ceramide.

This study investigates how different ORMDL isoforms regulate SPT activity and sphingolipid levels in response to ceramide, finding that each isoform has distinct sensitivity to ceramide.

Identification of ABHD6 as a regulator of lysophosphatidylserines in the mammalian liver and kidneys

The paper identifies ABHD6 as a lyso-PS lipase in the liver and kidneys, validating its enzymatic activity in vitro and in vivo.

LPA3: Pharmacodynamic differences between lysophosphatidic acid and oleoyl-methoxy glycerophosphothionate. Biased agonism, two sites.

The paper compares the pharmacodynamic effects of LPA and OMPT on LPA3 receptors, revealing differences in signaling, internalization, and refractory states, suggesting the existence of two binding sites.

Optical control of sphingolipid biosynthesis using photoswitchable sphingosines

This study introduces light-sensitive sphingosines (caSphs) that allow reversible control of sphingolipid biosynthesis through photo-isomerization, enabling precise manipulation of lipid production in living cells.

Unravelling neuronal and glial differences in ceramide composition, synthesis, and sensitivity to toxicity

The paper shows human iPSC-derived neurons and glia differ in ceramide synthesis, composition, and toxicity sensitivity, linking these differences to inflammation, ER stress, and apoptosis.

SMPD4 mediated sphingolipid metabolism regulates brain and primary cilia development

The paper investigates the role of SMPD4 in sphingolipid metabolism and its impact on brain and primary cilia development using a mouse model and human stem cells.