A5080068461- Lipid metabolism and biosynthesis
- Adipose Tissue and Metabolism
- Mitochondrial Function and Pathology
- Cancer, Lipids, and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Gut microbiota and health
- Advanced Proteomics Techniques and Applications
- Photosynthetic Processes and Mechanisms
- Mass Spectrometry Techniques and Applications
- Nanoparticles: synthesis and applications
- Liver Disease Diagnosis and Treatment
- Aquaculture disease management and microbiota
- Cholesterol and Lipid Metabolism
- Genetics, Aging, and Longevity in Model Organisms
- Diet and metabolism studies
- Electrochemical Analysis and Applications
- Genetic Neurodegenerative Diseases
- Analytical chemistry methods development
- RNA modifications and cancer
- Ferroptosis and cancer prognosis
- Identification and Quantification in Food
- Vibrio bacteria research studies
- Digestive system and related health
- Diet, Metabolism, and Disease
- Selenium in Biological Systems
The University of Texas Southwestern Medical Center
2015-2025
Southwestern Medical Center
2019-2025
Center for Human Genetics
2021
HumanN (United States)
2020-2021
Centro De Medicina Veterinária Anjos De Assis
2021
University of Lisbon
2015-2017
Instituto Politécnico de Lisboa
2011-2014
Rede de Química e Tecnologia
2005-2014
Instituto Superior Técnico
2011-2014
Universidade Nova de Lisboa
2005-2014
Abstract Mutant KRAS (KM), the most common oncogene in lung cancer (LC), regulates fatty acid (FA) metabolism. However, role of FA LC tumorigenesis is still not sufficiently characterized. Here, we show that KMLC has a specific lipid profile, with high triacylglycerides and phosphatidylcholines (PC). We demonstrate FASN, rate-limiting enzyme synthesis, while being dispensable EGFR-mutant or wild-type LC, required for viability cells. Integrating lipidomic, transcriptomic functional analyses,...
Diacylglycerol acyltransferase 2 (DGAT2) catalyzes the final step of triglyceride (TG) synthesis. DGAT2 deletion in mice lowers liver TGs, and inhibitors are under investigation for treatment fatty disease. Here, we show that inhibition also suppressed SREBP-1 cleavage, reduced acid synthesis, lowered TG accumulation secretion from liver. increased phosphatidylethanolamine (PE) levels endoplasmic reticulum (ER) inhibited while overexpression ER PE concentrations cleavage vivo. enrichment...
Significance Feedback control of cholesterol metabolism is essential for cell viability and prevention heart attacks. Cells acquire from receptor-mediated uptake low-density lipoprotein, which delivers to lysosomes. To exert feedback control, must reach the endoplasmic reticulum (ER). Here we use a CRISPR screen show that lysosome-derived moves first plasma membrane then ER. The last movement requires an enzyme produces phosphatidylserine. This demonstrates transmembrane one lipid...
Inborn errors of metabolism (IEMs) link metabolic defects to human phenotypes. Modern genomics has accelerated IEM discovery, but assessing the impact genomic variants is still challenging. Here, we integrate and metabolomics identify a cause lactic acidosis epilepsy. The proband compound heterozygote for in LIPT1, which encodes lipoyltransferase required 2-ketoacid dehydrogenase (2KDH) function. Metabolomics reveals abnormalities lipids, amino acids, 2-hydroxyglutarate consistent with loss...
Substitution of lysine for glutamic acid at residu 167 in Transmembrane 6 superfamily member 2 (TM6SF2) is associated with fatty liver disease and reduced plasma lipid levels. Tm6sf2-/- mice replicate the human phenotype but were not suitable detailed mechanistic studies. As an alternative model, we generated rats to determine subcellular location function TM6SF2.Two lines established using gene editing. Lipids from tissues newly secreted very low density lipoproteins (VLDLs) quantified...
An unbiased sample preparation free of interferents (i.e., competing analytes, detergents, plastics) is critical to any lipid MS workflow. Here we present a novel three-phase extraction (3PLE) technique using single-step liquid-liquid (LLE) that allows both and fractionation lipids by polarity. 3PLE composed one aqueous two organic phases. The upper phase enriched in neutral (triacylglycerols cholesteryl esters), while the middle contains major glycerophospholipids. Thin-layer...
Significance Atopic dermatitis (AD) is a chronic inflammatory skin condition affecting 13% of adults and 10% children worldwide. The inflammation seen in AD driven by type 2 cytokines, including IL-4 IL-13. We have an incomplete understanding about how these cytokines impact the epithelial barrier drive pathology. Our study demonstrates that IL-13 promote androgen production lipid abnormalities sebocytes. These findings deepen our immune system on epithelium.
Significance Cholesterol constitutes 50% of lipids in the plasma membrane (PM) animal cells. Sensors endoplasmic reticulum (ER) maintain this level by adjusting cholesterol uptake, synthesis, and storage. Uptake is mediated LDL receptors, which deliver cholesterol-carrying to lysosomes from moves PM then ER. We report PM-to-ER transport requires cholesterol-binding Aster proteins anchored ER phosphatidylserine embedded PM. Asters are known bind phosphatidylserine, accounts for part...
Significance The current study reveals the functions of FAF1 in protecting cells from ferroptosis, a novel cell death pathway triggered by PUFA peroxidation. In absence FAF1, cultured and mice are extremely sensitive to ferroptosis when exposed physiological levels PUFAs. Mechanistically, sequesters PUFAs into hydrophobic core global structure that limits their access positively charged Fe 2+ , which catalyzes peroxidation reaction. These observations suggest FAF1-mediated protection plays...
Cells adapt to cold by increasing levels of unsaturated phospholipids and membrane fluidity through conserved homeostatic mechanisms. Here we report an exceptionally large evolutionarily protein LPD-3 in C. elegans that mediates lipid trafficking confer resilience. We identify lpd-3 mutants a mutagenesis screen for genetic suppressors the desaturase FAT-7. bridges endoplasmic reticulum (ER) plasma membranes (PM), forming structurally predicted hydrophobic tunnel trafficking. exhibit abnormal...
Insulin-mechanistic target of rapamycin (mTOR) signaling drives anabolic growth during organismal development; its late-life dysregulation contributes to aging and limits lifespans. Age-related regulatory mechanisms functional consequences insulin-mTOR remain incompletely understood. Here, we identify LPD-3 as a megaprotein that orchestrates the tempo C. elegans aging. We find an agonist insulin, INS-7, is drastically overproduced from early life shortens lifespan in lpd-3 mutants. forms...
Abstract De novo lipogenesis (DNL) is disrupted in a wide range of human disease. Thus, quantification DNL may provide insight into mechanisms and guide interventions if it can be performed rapidly noninvasively. flux commonly measured by 2 H incorporation fatty acids following deuterated water ( O) administration. However, the sensitivity this approach limited natural abundance 13 C, which masks detection mass spectrometry. Here we report that high-resolution Orbitrap gas-chromatography...
Chronic inflammation in autoimmunity is driven by T cell hyperactivation. This unregulated response to self fuelled heightened metabolic programmes, which offers a promising new direction uncover novel treatment strategies. αβhydrolase domain–containing protein 11 (ABHD11) mitochondrial hydrolase that maintains the catalytic function of αketoglutarate dehydrogenase (αKGDH), and its expression CD4+ cells has been linked remission status rheumatoid arthritis (RA). However, importance ABHD11...