Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling
York AG, Williams KJ, Argus JP, Zhou QD, Brar G, Vergnes L, Gray EE, Zhen A, Wu NC, Yamada DH, Cunningham CR, Tarling EJ, Wilks MQ, Casero D, Gray DH, Yu AK, Wang ES, Brooks DG, Sun R, Kitchen SG, Wu TT, Reue K, Stetson DB, Bensinger SJ. Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling. Cell 2015, 163: 1716-1729. PMID: 26686653, PMCID: PMC4783382, DOI: 10.1016/j.cell.2015.11.045.Peer-Reviewed Original ResearchConceptsImport of cholesterolI interferonType I IFNsSTING-dependent mannerCholesterol biosynthetic pathwayI IFNsCombination of biosynthesisBiosynthetic fluxBiosynthetic pathwayLong-chain fatty acidsIsotope tracer analysisMetabolic shiftMetabolic pathwaysType I interferonCholesterol biosynthesisLipid requirementsChain fatty acidsInnate immunityBiosynthesisFatty acidsPool sizePathwayMechanistic studiesViral challengeFree cholesterolModulation of PICALM Levels Perturbs Cellular Cholesterol Homeostasis
Mercer J, Argus J, Crabtree D, Keenan M, Wilks M, Ashley J, Bensinger S, Lavau C, Wechsler D. Modulation of PICALM Levels Perturbs Cellular Cholesterol Homeostasis. PLOS ONE 2015, 10: e0129776. PMID: 26075887, PMCID: PMC4467867, DOI: 10.1371/journal.pone.0129776.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsGenome-wide association studiesClathrin-mediated endocytosisCellular cholesterol homeostasisGene expression studiesExpression of genesPICALM expressionHeterologous proteinsEncode proteinsAssociation studiesPICALMNucleotide polymorphismsChromosomal translocationsExpressed proteinsCholesterol biosynthesisModulate macroautophagyCholesterol homeostasisBiological rolePathway analysisFlow cytometry analysisLDLR expressionLDL receptorLevels of LDLR expressionAlzheimer's diseasePool size