{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:04:53Z","timestamp":1788519893398,"version":"build-2803163510"},"reference-count":82,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T00:00:00Z","timestamp":1596672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008385","name":"Fondazione per la Ricerca sulla Fibrosi Cistica","doi-asserted-by":"publisher","award":["FFC#11-2016"],"award-info":[{"award-number":["FFC#11-2016"]}],"id":[{"id":"10.13039\/501100008385","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cystic fibrosis (CF) is a hereditary disease, with 70% of patients developing a proteinopathy related to the deletion of phenylalanine 508. CF is associated with multiple organ dysfunction, chronic inflammation, and recurrent lung infections. CF is characterized by defective autophagy, lipid metabolism, and immune response. Intracellular lipid accumulation favors microbial infection, and autophagy deficiency impairs internalized pathogen clearance. Myriocin, an inhibitor of sphingolipid synthesis, significantly reduces inflammation, promotes microbial clearance in the lungs, and induces autophagy and lipid oxidation. RNA-seq was performed in Aspergillusfumigatus-infected and myriocin-treated CF patients\u2019 derived monocytes and in a CF bronchial epithelial cell line. Fungal clearance was also evaluated in CF monocytes. Myriocin enhanced CF patients\u2019 monocytes killing of A. fumigatus. CF patients\u2019 monocytes and cell line responded to infection with a profound transcriptional change; myriocin regulates genes that are involved in inflammation, autophagy, lipid storage, and metabolism, including histones and heat shock proteins whose activity is related to the response to infection. We conclude that the regulation of sphingolipid synthesis induces a metabolism drift by promoting autophagy and lipid consumption. This process is driven by a transcriptional program that corrects part of the differences between CF and control samples, therefore ameliorating the infection response and pathogen clearance in the CF cell line and in CF peripheral blood monocytes.<\/jats:p>","DOI":"10.3390\/cells9081845","type":"journal-article","created":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T09:41:21Z","timestamp":1596706881000},"page":"1845","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Cystic Fibrosis Defective Response to Infection Involves Autophagy and Lipid Metabolism"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8008-0191","authenticated-orcid":false,"given":"Alessandra","family":"Mingione","sequence":"first","affiliation":[{"name":"Biochemistry and Molecular Biology Laboratory, Health Science Department, University of Milan, San Paolo Hospital, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emerenziana","family":"Ottaviano","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Microbiology, Health Science Department, University of Milan, San Paolo Hospital, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Barcella","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Microbiology, Health Science Department, University of Milan, San Paolo Hospital, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Merelli","sequence":"additional","affiliation":[{"name":"National Research Council of Italy, Institute for Biomedical Technologies, Via Fratelli Cervi 93, 20090 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Rosso","sequence":"additional","affiliation":[{"name":"Health Sciences Department, University of Milan, Thoracic surgery and transplantation Unit, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Armeni","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Section of Biochemistry, Biology and Physics, Polytechnic University of Marche, 60131 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Cirilli","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Referral Care Center, Mother-Child Department, United Hospitals Le Torrette, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Ghidoni","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Laboratory, Health Science Department, University of Milan, San Paolo Hospital, 20142 Milan, Italy"},{"name":"\u201cAldo Ravelli\u201d Center for Neurotechnology and Experimental Brain Therapeutics, via Antonio di Rudin\u00ec 8, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1893-0455","authenticated-orcid":false,"given":"Elisa","family":"Borghi","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Microbiology, Health Science Department, University of Milan, San Paolo Hospital, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2368-2393","authenticated-orcid":false,"given":"Paola","family":"Signorelli","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Laboratory, Health Science Department, University of Milan, San Paolo Hospital, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1515\/cclm-2015-1151","article-title":"Reduced absorption and enhanced synthesis of cholesterol in patients with cystic fibrosis: A preliminary study of plasma sterols","volume":"54","author":"Gelzo","year":"2016","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1093\/ajcn\/75.6.1005","article-title":"Abnormal lipid concentrations in cystic fibrosis","volume":"75","author":"Figueroa","year":"2002","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.4161\/auto.21483","article-title":"Targeting autophagy as a novel strategy for facilitating the therapeutic action of potentiators on DeltaF508 cystic fibrosis transmembrane conductance regulator","volume":"8","author":"Luciani","year":"2012","journal-title":"Autophagy"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/nm1748","article-title":"Ceramide accumulation mediates inflammation, cell death and infection susceptibility in cystic fibrosis","volume":"14","author":"Teichgraber","year":"2008","journal-title":"Nat. Med."},{"key":"ref_5","first-page":"110","article-title":"Inhibition of Sphingolipid Synthesis as a Phenotype-Modifying Therapy in Cystic Fibrosis","volume":"54","author":"Mingione","year":"2020","journal-title":"Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ccm.2015.11.010","article-title":"Innate and Adaptive Immunity in Cystic Fibrosis","volume":"37","author":"Bruscia","year":"2016","journal-title":"Clin. Chest Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"17066","DOI":"10.1038\/s41598-018-35151-7","article-title":"Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have differential effects on cystic fibrosis macrophage function","volume":"8","author":"Zhang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/j.bbagen.2016.02.014","article-title":"Inhibition of ceramide de novo synthesis by myriocin produces the double effect of reducing pathological inflammation and exerting antifungal activity against A. fumigatus airways infection","volume":"1860","author":"Caretti","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.jcf.2016.10.011","article-title":"The impact of impaired macrophage functions in cystic fibrosis disease progression","volume":"16","author":"Leveque","year":"2017","journal-title":"J. Cyst. Fibros."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S75","DOI":"10.1002\/ppul.24126","article-title":"The myriad challenges of respiratory fungal infection in cystic fibrosis","volume":"53","author":"Tracy","year":"2018","journal-title":"Pediatr. Pulmonol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1164\/rccm.201106-1027OC","article-title":"Cystic fibrosis transmembrane conductance regulator regulates epithelial cell response to Aspergillus and resultant pulmonary inflammation","volume":"185","author":"Chaudhary","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3389\/fphar.2019.00020","article-title":"Adapting Proteostasis and Autophagy for Controlling the Pathogenesis of Cystic Fibrosis Lung Disease","volume":"10","author":"Bodas","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"104","DOI":"10.4161\/auto.7.1.13987","article-title":"Cystic fibrosis: A disorder with defective autophagy","volume":"7","author":"Luciani","year":"2011","journal-title":"Autophagy"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s40348-016-0040-z","article-title":"Manipulating proteostasis to repair the F508del-CFTR defect in cystic fibrosis","volume":"3","author":"Esposito","year":"2016","journal-title":"Mol. Cell. Pediatr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"118","DOI":"10.3389\/fcell.2018.00118","article-title":"The Interplay of Host Autophagy and Eukaryotic Pathogens","volume":"6","author":"Evans","year":"2018","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.2217\/fmb-2018-0013","article-title":"Lipid metabolism and intracellular bacterial virulence: Key to next-generation therapeutics","volume":"13","author":"Rameshwaram","year":"2018","journal-title":"Future Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1002\/iub.1737","article-title":"The role of lipids in host-pathogen interactions","volume":"70","author":"Walpole","year":"2018","journal-title":"IUBMB Life"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.funbio.2017.07.003","article-title":"Lipid biology in fungal stress and virulence: Entomopathogenic fungi","volume":"122","author":"Keyhani","year":"2018","journal-title":"Fungal Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3283","DOI":"10.4049\/jimmunol.1601920","article-title":"PPAR-alpha Activation Mediates Innate Host Defense through Induction of TFEB and Lipid Catabolism","volume":"198","author":"Kim","year":"2017","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1194\/jlr.P013722","article-title":"Plasma lipidomics reveals potential prognostic signatures within a cohort of cystic fibrosis patients","volume":"52","author":"Ollero","year":"2011","journal-title":"J. Lipid Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.jcf.2004.05.022","article-title":"Methods for the study of lipid metabolites in cystic fibrosis","volume":"3","author":"Ollero","year":"2004","journal-title":"J. Cyst. Fibros. Soc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.bbrc.2013.03.032","article-title":"Ceramide mediates lung fibrosis in cystic fibrosis","volume":"434","author":"Ziobro","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/1465-9921-11-61","article-title":"Increased plasma membrane cholesterol in cystic fibrosis cells correlates with CFTR genotype and depends on de novo cholesterol synthesis","volume":"11","author":"Fang","year":"2010","journal-title":"Respir. Res."},{"key":"ref_24","first-page":"605","article-title":"Cystic fibrosis: From protein-energy malnutrition to obesity with dyslipidemia","volume":"23","author":"Sawamura","year":"2013","journal-title":"Iran. J. Pediatr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.bbagen.2013.10.018","article-title":"Anti-inflammatory action of lipid nanocarrier-delivered myriocin: Therapeutic potential in cystic fibrosis","volume":"1840","author":"Caretti","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1007\/s00210-017-1373-4","article-title":"Myriocin treatment of CF lung infection and inflammation: Complex analyses for enigmatic lipids","volume":"390","author":"Caretti","year":"2017","journal-title":"Naunyn-Schmiedeberg Arch. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/j.1365-2567.2004.02076.x","article-title":"Human monocyte isolation methods influence cytokine production from in vitro generated dendritic cells","volume":"114","author":"Elkord","year":"2005","journal-title":"Immunology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: An efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: An R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"Omics J. Integr. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1084\/jem.108.6.925","article-title":"Bactericidal action of histone","volume":"108","author":"Hirsch","year":"1958","journal-title":"J. Exp. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e00003","DOI":"10.7554\/eLife.00003","article-title":"A novel role for lipid droplets in the organismal antibacterial response","volume":"1","author":"Anand","year":"2012","journal-title":"Elife"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3268","DOI":"10.4049\/jimmunol.165.6.3268","article-title":"Pepsin-mediated processing of the cytoplasmic histone H2A to strong antimicrobial peptide buforin I","volume":"165","author":"Kim","year":"2000","journal-title":"J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/0006-2952(95)00142-M","article-title":"Extra-nuclear location of histones in activated human peripheral blood lymphocytes and cultured T-cells","volume":"50","author":"Watson","year":"1995","journal-title":"Biochem. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1242\/jcs.96.3.461","article-title":"Cytoplasmic pool of histone H1 in mammalian cells","volume":"96 Pt 3","author":"Zlatanova","year":"1990","journal-title":"J. Cell Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6933","DOI":"10.1021\/jf201646x","article-title":"Antifungal properties of wheat histones (H1-H4) and purified wheat histone H1","volume":"59","author":"Heden","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1080\/15548627.2015.1017184","article-title":"Binding of the pathogen receptor HSP90AA1 to avibirnavirus VP2 induces autophagy by inactivating the AKT-MTOR pathway","volume":"11","author":"Hu","year":"2015","journal-title":"Autophagy"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/jcb.27378","article-title":"PNPLA3 variant M148 causes resistance to starvation-mediated lipid droplet autophagy in human hepatocytes","volume":"120","author":"Negoita","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/978-1-59745-157-4_4","article-title":"LC3 and Autophagy","volume":"445","author":"Tanida","year":"2008","journal-title":"Methods Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Hu, F., Shao, L., Zhang, J., Zhang, H., Wen, A., and Zhang, P. (2020). Knockdown of ZFAS1 Inhibits Hippocampal Neurons Apoptosis and Autophagy by Activating the PI3K\/AKT Pathway via Up-regulating miR-421 in Epilepsy. Neurochem. Res.","DOI":"10.1007\/s11064-020-03103-1"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5747","DOI":"10.1128\/MCB.02070-07","article-title":"The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane","volume":"28","author":"Bandyopadhyay","year":"2008","journal-title":"Mol. Cell. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1002\/ppul.21026","article-title":"IL1B polymorphisms modulate cystic fibrosis lung disease","volume":"44","author":"Levy","year":"2009","journal-title":"Pediatr. Pulmonol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3691","DOI":"10.1074\/jbc.C112.430298","article-title":"Analysis of human bronchial epithelial cell proinflammatory response to Burkholderia cenocepacia infection: Inability to secrete il-1beta","volume":"288","author":"Gillette","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/emboj.2013.8","article-title":"TMEM59 defines a novel ATG16L1-binding motif that promotes local activation of LC3","volume":"32","author":"Letek","year":"2013","journal-title":"EMBO J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1091\/mbc.e08-07-0671","article-title":"The TP53INP2 protein is required for autophagy in mammalian cells","volume":"20","author":"Nowak","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/ng.3256","article-title":"Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and lysosome-autophagosome dysfunction","volume":"47","author":"Akizu","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1093\/hmg\/ddy101","article-title":"SNX14 mutations affect endoplasmic reticulum-associated neutral lipid metabolism in autosomal recessive spinocerebellar ataxia 20","volume":"27","author":"Bryant","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_51","first-page":"6051262","article-title":"Higd1a Protects Cells from Lipotoxicity under High-Fat Exposure","volume":"2019","author":"Li","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.jss.2015.06.059","article-title":"Inhibition of lipogenesis reduces inflammation and organ injury in sepsis","volume":"200","author":"Idrovo","year":"2016","journal-title":"J. Surg. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"G1239","DOI":"10.1152\/ajpgi.00206.2009","article-title":"CFTR knockdown stimulates lipid synthesis and transport in intestinal Caco-2\/15 cells","volume":"297","author":"Mailhot","year":"2009","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"pe39","DOI":"10.1126\/scisignal.2002355","article-title":"TBK1 mediates crosstalk between the innate immune response and autophagy","volume":"4","author":"Weidberg","year":"2011","journal-title":"Sci. Signal."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1080\/15548627.2017.1389824","article-title":"Autophagy and innate immunity: Insights from invertebrate model organisms","volume":"14","author":"Kuo","year":"2018","journal-title":"Autophagy"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/s41467-020-14533-4","article-title":"TBC1D9 regulates TBK1 activation through Ca2+ signaling in selective autophagy","volume":"11","author":"Nozawa","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jcf.2009.09.002","article-title":"Prevalence of dyslipidemia in adults with cystic fibrosis","volume":"9","author":"Rhodes","year":"2010","journal-title":"J. Cyst. Fibros."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.jcf.2012.08.012","article-title":"Hypertriglyceridemia is associated with insulin levels in adult cystic fibrosis patients","volume":"12","author":"Ishimo","year":"2013","journal-title":"J. Cyst. Fibros."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1056\/NEJMoa021218","article-title":"Association of cystic fibrosis with abnormalities in fatty acid metabolism","volume":"350","author":"Freedman","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1079\/BJN20051655","article-title":"Serum phospholipid fatty acid profile and dietary intake in an adult Mediterranean population with cystic fibrosis","volume":"96","author":"Olveira","year":"2006","journal-title":"Br. J. Nutr."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"G609","DOI":"10.1152\/ajpgi.00332.2005","article-title":"Abnormal intracellular lipid processing contributes to fat malabsorption in cystic fibrosis patients","volume":"290","author":"Peretti","year":"2006","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/1479-5876-11-109","article-title":"Nutrition in calcium nephrolithiasis","volume":"11","author":"Dogliotti","year":"2013","journal-title":"J. Transl. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"L476","DOI":"10.1152\/ajplung.00262.2006","article-title":"Altered cholesterol homeostasis in cultured and in vivo models of cystic fibrosis","volume":"292","author":"White","year":"2007","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.biocel.2014.01.026","article-title":"Localized lipidomics in cystic fibrosis: TOF-SIMS imaging of lungs from Pseudomonas aeruginosa-infected mice","volume":"52","author":"Desbenoit","year":"2014","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1242\/jcs.03350","article-title":"Misassembled mutant DeltaF508 CFTR in the distal secretory pathway alters cellular lipid trafficking","volume":"120","author":"Gentzsch","year":"2007","journal-title":"J. Cell Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.1091\/mbc.e04-03-0176","article-title":"Endocytic trafficking routes of wild type and DeltaF508 cystic fibrosis transmembrane conductance regulator","volume":"15","author":"Gentzsch","year":"2004","journal-title":"Mol. Biol. Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"L791","DOI":"10.1152\/ajplung.00167.2014","article-title":"Impaired TLR4 and HIF expression in cystic fibrosis bronchial epithelial cells downregulates hemeoxygenase-1 and alters iron homeostasis in vitro","volume":"307","author":"Chillappagari","year":"2014","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.cca.2019.08.015","article-title":"Heat shock proteins in infection","volume":"498","author":"Bolhassani","year":"2019","journal-title":"Clin. Chim. Acta Int. J. Clin. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.coi.2004.05.007","article-title":"Heat-shock proteins and the host-pathogen interaction during bacterial infection","volume":"16","author":"Stewart","year":"2004","journal-title":"Curr. Opin. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00430-007-0055-0","article-title":"Heat shock proteins: Linking danger and pathogen recognition","volume":"197","author":"Osterloh","year":"2008","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1080\/15548627.2015.1009776","article-title":"Heat shock response and autophagy--cooperation and control","volume":"11","author":"Dokladny","year":"2015","journal-title":"Autophagy"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1126\/science.2799391","article-title":"A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins","volume":"246","author":"Chiang","year":"1989","journal-title":"Science"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1126\/science.273.5274.501","article-title":"A receptor for the selective uptake and degradation of proteins by lysosomes","volume":"273","author":"Cuervo","year":"1996","journal-title":"Science"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/nature10317","article-title":"Molecular chaperones in protein folding and proteostasis","volume":"475","author":"Hartl","year":"2011","journal-title":"Nature"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Tardelli, M., Bruschi, F.V., and Trauner, M. (2020). The role of metabolic lipases in the pathogenesis and management of liver disease. Hepatology.","DOI":"10.1002\/hep.31250"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"986","DOI":"10.3389\/fphys.2019.00986","article-title":"Sphingolipid Synthesis Inhibition by Myriocin Administration Enhances Lipid Consumption and Ameliorates Lipid Response to Myocardial Ischemia Reperfusion Injury","volume":"10","author":"Bonezzi","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.tem.2016.07.005","article-title":"Sphingolipid De Novo Biosynthesis: A Rheostat of Cardiovascular Homeostasis","volume":"27","author":"Sasset","year":"2016","journal-title":"Trends Endocrinol. Metab. TEM"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1194\/jlr.M065920","article-title":"ORMDL proteins regulate ceramide levels during sterile inflammation","volume":"57","author":"Cai","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1080\/13543784.2019.1657825","article-title":"Acetyl-CoA carboxylase (ACC) as a therapeutic target for metabolic syndrome and recent developments in ACC1\/2 inhibitors","volume":"28","author":"Chen","year":"2019","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Ammanathan, V., Mishra, P., Chavalmane, A.K., Muthusamy, S., Jadhav, V., Siddamadappa, C., and Manjithaya, R. (2019). Restriction of intracellular Salmonella replication by restoring TFEB-mediated xenophagy. Autophagy, 1\u201314.","DOI":"10.1080\/15548627.2019.1689770"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1007\/s10620-017-4700-1","article-title":"The Clinical Implications of Fatty Pancreas: A Concise Review","volume":"62","author":"Khoury","year":"2017","journal-title":"Dig. Dis. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1148\/radiology.179.1.2006275","article-title":"Cystic fibrosis: MR imaging of the pancreas","volume":"179","author":"Tham","year":"1991","journal-title":"Radiology"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/8\/1845\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:57:10Z","timestamp":1760176630000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/8\/1845"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,6]]},"references-count":82,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["cells9081845"],"URL":"https:\/\/doi.org\/10.3390\/cells9081845","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,6]]}}}