{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:13:02Z","timestamp":1790615582073,"version":"4.1.0"},"reference-count":73,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T00:00:00Z","timestamp":1606348800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T00:00:00Z","timestamp":1606348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>ACBD5 deficiency is a novel peroxisome disorder with a largely uncharacterized pathology. ACBD5 was recently identified in a tethering complex mediating membrane contacts between peroxisomes and the endoplasmic reticulum (ER). An ACBD5-deficient mouse was analyzed to correlate ACBD5 tethering functions with the disease phenotype. ACBD5-deficient mice exhibit elevated very long-chain fatty acid levels and a progressive cerebellar pathology. Liver did not exhibit pathologic changes but increased peroxisome abundance and drastically reduced peroxisome-ER contacts. Lipidomics of liver and cerebellum revealed tissue-specific alterations in distinct lipid classes and subspecies. In line with the neurological pathology, unusual ultra-long chain fatty acids (C\u2009&gt;\u200932) were elevated in phosphocholines from cerebelli but not liver indicating an organ-specific imbalance in fatty acid degradation and elongation pathways. By contrast, ether lipid formation was perturbed in liver towards an accumulation of alkyldiacylglycerols. The alterations in several lipid classes suggest that ACBD5, in addition to its acyl-CoA binding function, might maintain peroxisome-ER contacts in order to contribute to the regulation of anabolic and catabolic cellular lipid pathways.<\/jats:p>","DOI":"10.1038\/s42003-020-01442-x","type":"journal-article","created":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T06:03:50Z","timestamp":1606370630000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Cerebellar and hepatic alterations in ACBD5-deficient mice are associated with unexpected, distinct alterations in cellular lipid homeostasis"],"prefix":"10.1038","volume":"3","author":[{"given":"Warda","family":"Darwisch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marino","family":"von Spangenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Lehmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6znur","family":"Singin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geralt","family":"Deubert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"K\u00fchl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Roos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Horstmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"K\u00f6rber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Hoppe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kuner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia L.","family":"Pras-Raves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine H. C.","family":"van Kampen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans R.","family":"Waterham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin V.","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen G.","family":"Okun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Schultz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9048-1041","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric M.","family":"Vaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8881-0902","authenticated-orcid":false,"given":"Markus","family":"Islinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,26]]},"reference":[{"key":"1442_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09253-3","volume":"10","author":"L Scorrano","year":"2019","unstructured":"Scorrano, L. et al. Coming together to define membrane contact sites. Nat. Commun. 10, 1287 (2019).","journal-title":"Nat. Commun."},{"key":"1442_CR2","doi-asserted-by":"publisher","first-page":"23055","DOI":"10.1074\/jbc.M610910200","volume":"282","author":"M Islinger","year":"2007","unstructured":"Islinger, M., Luers, G. H., Li, K. W., Loos, M. & Volkl, A. Rat liver peroxisomes after fibrate treatment. A survey using quantitative mass spectrometry. J. Biol. Chem. 282, 23055\u201323069 (2007).","journal-title":"J. Biol. Chem."},{"key":"1442_CR3","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1074\/mcp.M700169-MCP200","volume":"6","author":"S Wiese","year":"2007","unstructured":"Wiese, S. et al. Proteomics characterization of mouse kidney peroxisomes by tandem mass spectrometry and protein correlation profiling. Mol. Cell Proteom. 6, 2045\u20132057 (2007).","journal-title":"Mol. Cell Proteom."},{"key":"1442_CR4","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1242\/jcs.200204","volume":"130","author":"JL Costello","year":"2017","unstructured":"Costello, J. L. et al. Predicting the targeting of tail-anchored proteins to subcellular compartments in mammalian cells. J. Cell Sci. 130, 1675\u20131687 (2017).","journal-title":"J. Cell Sci."},{"key":"1442_CR5","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1083\/jcb.201607055","volume":"216","author":"JL Costello","year":"2017","unstructured":"Costello, J. L. et al. ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER. J. Cell Biol. 216, 331\u2013342 (2017).","journal-title":"J. Cell Biol."},{"key":"1442_CR6","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1083\/jcb.201608128","volume":"216","author":"R Hua","year":"2017","unstructured":"Hua, R. et al. VAPs and ACBD5 tether peroxisomes to the ER for peroxisome maintenance and lipid homeostasis. J. Cell Biol. 216, 367\u2013377 (2017).","journal-title":"J. Cell Biol."},{"key":"1442_CR7","doi-asserted-by":"publisher","unstructured":"Schrader, M., Kamoshita, M. & Islinger, M. Organelle interplay-peroxisome interactions in health and disease. J. Inherit. Metab. Dis. https:\/\/doi.org\/10.1002\/jimd.12083 (2019).","DOI":"10.1002\/jimd.12083"},{"key":"1442_CR8","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1101\/gr.144105.112","volume":"23","author":"L Abu-Safieh","year":"2013","unstructured":"Abu-Safieh, L. et al. Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes. Genome Res. 23, 236\u2013247 (2013).","journal-title":"Genome Res."},{"key":"1442_CR9","doi-asserted-by":"publisher","unstructured":"Ferdinandusse, S. et al. ACBD5 deficiency causes a defect in peroxisomal very long-chain fatty acid metabolism. J. Med. Genet. https:\/\/doi.org\/10.1136\/jmedgenet-2016-104132 (2016).","DOI":"10.1136\/jmedgenet-2016-104132"},{"key":"1442_CR10","doi-asserted-by":"publisher","first-page":"2863","DOI":"10.1194\/jlr.R005959","volume":"51","author":"PP Van Veldhoven","year":"2010","unstructured":"Van Veldhoven, P. P. Biochemistry and genetics of inherited disorders of peroxisomal fatty acid metabolism. J. Lipid Res. 51, 2863\u20132895 (2010).","journal-title":"J. Lipid Res."},{"key":"1442_CR11","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1074\/jbc.M116.760090","volume":"292","author":"Y Yagita","year":"2017","unstructured":"Yagita, Y. et al. Deficiency of a retinal dystrophy protein, acyl-CoA binding domain-containing 5 (ACBD5), impairs peroxisomal beta-oxidation of very-long-chain fatty acids. J. Biol. Chem. 292, 691\u2013705 (2017).","journal-title":"J. Biol. Chem."},{"key":"1442_CR12","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1007\/978-981-13-2233-4_15","volume":"89","author":"RJA Wanders","year":"2018","unstructured":"Wanders, R. J. A., Waterham, H. R. & Ferdinandusse, S. Peroxisomes and their central role in metabolic interaction networks in humans. Subcell. Biochem. 89, 345\u2013365 (2018).","journal-title":"Subcell. Biochem."},{"key":"1442_CR13","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1080\/15384101.2017.1314422","volume":"16","author":"JL Costello","year":"2017","unstructured":"Costello, J. L., Castro, I. G., Schrader, T. A., Islinger, M. & Schrader, M. Peroxisomal ACBD4 interacts with VAPB and promotes ER-peroxisome associations. Cell Cycle 16, 1039\u20131045 (2017).","journal-title":"Cell Cycle"},{"key":"1442_CR14","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1242\/jcs.087452","volume":"125","author":"A Itoyama","year":"2012","unstructured":"Itoyama, A. et al. Docosahexaenoic acid mediates peroxisomal elongation, a prerequisite for peroxisome division. J. Cell Sci. 125, 589\u2013602 (2012).","journal-title":"J. Cell Sci."},{"key":"1442_CR15","doi-asserted-by":"publisher","unstructured":"Guyenet, S. J. et al. A simple composite phenotype scoring system for evaluating mouse models of cerebellar ataxia. J. Vis. Exp. https:\/\/doi.org\/10.3791\/1787 (2010).","DOI":"10.3791\/1787"},{"key":"1442_CR16","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.pneurobio.2007.07.007","volume":"83","author":"S Saxena","year":"2007","unstructured":"Saxena, S. & Caroni, P. Mechanisms of axon degeneration: from development to disease. Prog. Neurobiol. 83, 174\u2013191 (2007).","journal-title":"Prog. Neurobiol."},{"key":"1442_CR17","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.bbadis.2015.11.014","volume":"1862","author":"M Pekny","year":"2016","unstructured":"Pekny, M. & Pekna, M. Reactive gliosis in the pathogenesis of CNS diseases. Biochim. Biophys. Acta 1862, 483\u2013491 (2016).","journal-title":"Biochim. Biophys. Acta"},{"key":"1442_CR18","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.1016\/j.jmb.2019.01.016","volume":"431","author":"A Ferro","year":"2019","unstructured":"Ferro, A., Sheeler, C., Rosa, J. G. & Cvetanovic, M. Role of microglia in ataxias. J. Mol. Biol. 431, 1792\u20131804 (2019).","journal-title":"J. Mol. Biol."},{"key":"1442_CR19","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1002\/glia.22350","volume":"61","author":"C Cunningham","year":"2013","unstructured":"Cunningham, C. Microglia and neurodegeneration: the role of systemic inflammation. Glia 61, 71\u201390 (2013).","journal-title":"Glia"},{"key":"1442_CR20","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1111\/bpa.12290","volume":"25","author":"S De Munter","year":"2015","unstructured":"De Munter, S., Verheijden, S., Regal, L. & Baes, M. Peroxisomal disorders: a review on cerebellar pathologies. Brain Pathol. 25, 663\u2013678 (2015).","journal-title":"Brain Pathol."},{"key":"1442_CR21","doi-asserted-by":"publisher","first-page":"250","DOI":"10.3389\/fncel.2016.00250","volume":"10","author":"R Yamada","year":"2016","unstructured":"Yamada, R. & Kuba, H. Structural and functional plasticity at the axon initial segment. Front Cell Neurosci. 10, 250 (2016).","journal-title":"Front Cell Neurosci."},{"key":"1442_CR22","doi-asserted-by":"publisher","first-page":"7272","DOI":"10.1523\/JNEUROSCI.4747-14.2015","volume":"35","author":"MS Hamada","year":"2015","unstructured":"Hamada, M. S. & Kole, M. H. Myelin loss and axonal ion channel adaptations associated with gray matter neuronal hyperexcitability. J. Neurosci. 35, 7272\u20137286 (2015).","journal-title":"J. Neurosci."},{"key":"1442_CR23","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1002\/glia.22991","volume":"64","author":"KC Clark","year":"2016","unstructured":"Clark, K. C. et al. Compromised axon initial segment integrity in EAE is preceded by microglial reactivity and contact. Glia 64, 1190\u20131209 (2016).","journal-title":"Glia"},{"key":"1442_CR24","doi-asserted-by":"publisher","first-page":"45","DOI":"10.3389\/fncel.2017.00045","volume":"11","author":"MS Hamada","year":"2017","unstructured":"Hamada, M. S., Popovic, M. A. & Kole, M. H. Loss of saltation and presynaptic action potential failure in demyelinated axons. Front Cell Neurosci. 11, 45 (2017).","journal-title":"Front Cell Neurosci."},{"key":"1442_CR25","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.neuroscience.2017.07.035","volume":"368","author":"N Jamann","year":"2018","unstructured":"Jamann, N., Jordan, M. & Engelhardt, M. Activity-dependent axonal plasticity in sensory systems. Neuroscience 368, 268\u2013282 (2018).","journal-title":"Neuroscience"},{"key":"1442_CR26","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.eplepsyres.2013.03.004","volume":"105","author":"RC Harty","year":"2013","unstructured":"Harty, R. C. et al. Axon initial segment structural plasticity in animal models of genetic and acquired epilepsy. Epilepsy Res. 105, 272\u2013279 (2013).","journal-title":"Epilepsy Res."},{"key":"1442_CR27","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1016\/j.bbamcr.2015.09.035","volume":"1863","author":"M Baes","year":"2016","unstructured":"Baes, M. & Van Veldhoven, P. P. Hepatic dysfunction in peroxisomal disorders. Biochim. Biophys. Acta 1863, 956\u2013970 (2016).","journal-title":"Biochim. Biophys. Acta"},{"key":"1442_CR28","doi-asserted-by":"publisher","first-page":"19228","DOI":"10.1074\/jbc.274.27.19228","volume":"274","author":"T Hashimoto","year":"1999","unstructured":"Hashimoto, T. et al. Peroxisomal and mitochondrial fatty acid beta-oxidation in mice nullizygous for both peroxisome proliferator-activated receptor alpha and peroxisomal fatty acyl-CoA oxidase. Genotype correlation with fatty liver phenotype. J. Biol. Chem. 274, 19228\u201319236 (1999).","journal-title":"J. Biol. Chem."},{"key":"1442_CR29","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1146\/annurev.cellbio.12.1.335","volume":"12","author":"T Lemberger","year":"1996","unstructured":"Lemberger, T., Desvergne, B. & Wahli, W. Peroxisome proliferator-activated receptors: a nuclear receptor signaling pathway in lipid physiology. Annu. Rev. Cell Dev. Biol. 12, 335\u2013363 (1996).","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"1442_CR30","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/1043-2760(93)90048-J","volume":"4","author":"H Keller","year":"1993","unstructured":"Keller, H. & Wahli, W. Peroxisome proliferator-activated receptors A link between endocrinology and nutrition? Trends Endocrinol. Metab. 4, 291\u2013296 (1993).","journal-title":"Trends Endocrinol. Metab."},{"key":"1442_CR31","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1194\/jlr.M400335-JLR200","volume":"46","author":"Y Wang","year":"2005","unstructured":"Wang, Y. et al. Tissue-specific, nutritional, and developmental regulation of rat fatty acid elongases. J. Lipid Res. 46, 706\u2013715 (2005).","journal-title":"J. Lipid Res."},{"key":"1442_CR32","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1038\/nature22369","volume":"546","author":"AM Valm","year":"2017","unstructured":"Valm, A. M. et al. Applying systems-level spectral imaging and analysis to reveal the organelle interactome. Nature 546, 162\u2013167 (2017).","journal-title":"Nature"},{"key":"1442_CR33","doi-asserted-by":"publisher","first-page":"e35172","DOI":"10.1371\/journal.pone.0035172","volume":"7","author":"H Horstmann","year":"2012","unstructured":"Horstmann, H., Korber, C., Satzler, K., Aydin, D. & Kuner, T. Serial section scanning electron microscopy (S3EM) on silicon wafers for ultra-structural volume imaging of cells and tissues. PLoS ONE 7, e35172 (2012).","journal-title":"PLoS ONE"},{"key":"1442_CR34","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/0005-2736(87)90321-X","volume":"897","author":"K Zaar","year":"1987","unstructured":"Zaar, K., Volkl, A. & Fahimi, H. D. Association of isolated bovine kidney cortex peroxisomes with endoplasmic reticulum. Biochim. Biophys. Acta 897, 135\u2013142 (1987).","journal-title":"Biochim. Biophys. Acta"},{"key":"1442_CR35","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1007\/s10545-017-0076-9","volume":"41","author":"K Herzog","year":"2018","unstructured":"Herzog, K. et al. Functional characterisation of peroxisomal beta-oxidation disorders in fibroblasts using lipidomics. J. Inherit. Metab. Dis. 41, 479\u2013487 (2018).","journal-title":"J. Inherit. Metab. Dis."},{"key":"1442_CR36","doi-asserted-by":"publisher","first-page":"3382","DOI":"10.1093\/brain\/awz291","volume":"142","author":"FM Vaz","year":"2019","unstructured":"Vaz, F. M. et al. Mutations in PCYT2 disrupt etherlipid biosynthesis and cause a complex hereditary spastic paraplegia. Brain 142, 3382\u20133397 (2019).","journal-title":"Brain"},{"key":"1442_CR37","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1194\/jlr.M600413-JLR200","volume":"48","author":"R Bartz","year":"2007","unstructured":"Bartz, R. et al. Lipidomics reveals that adiposomes store ether lipids and mediate phospholipid traffic. J. Lipid Res. 48, 837\u2013847 (2007).","journal-title":"J. Lipid Res."},{"key":"1442_CR38","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.lfs.2018.04.049","volume":"203","author":"RK Saini","year":"2018","unstructured":"Saini, R. K. & Keum, Y. S. Omega-3 and omega-6 polyunsaturated fatty acids: dietary sources, metabolism, and significance\u2014a review. Life Sci. 203, 255\u2013267 (2018).","journal-title":"Life Sci."},{"key":"1442_CR39","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.2353\/ajpath.2006.041220","volume":"168","author":"S Huyghe","year":"2006","unstructured":"Huyghe, S. et al. Peroxisomal multifunctional protein-2 deficiency causes motor deficits and glial lesions in the adult central nervous system. Am. J. Pathol. 168, 1321\u20131334 (2006).","journal-title":"Am. J. Pathol."},{"key":"1442_CR40","doi-asserted-by":"publisher","first-page":"16329","DOI":"10.1074\/jbc.M001994200","volume":"275","author":"M Baes","year":"2000","unstructured":"Baes, M. et al. Inactivation of the peroxisomal multifunctional protein-2 in mice impedes the degradation of not only 2-methyl-branched fatty acids and bile acid intermediates but also of very long chain fatty acids. J. Biol. Chem. 275, 16329\u201316336 (2000).","journal-title":"J. Biol. Chem."},{"key":"1442_CR41","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.nbd.2013.06.006","volume":"58","author":"S Verheijden","year":"2013","unstructured":"Verheijden, S. et al. Peroxisomal multifunctional protein-2 deficiency causes neuroinflammation and degeneration of Purkinje cells independent of very long chain fatty acid accumulation. Neurobiol. Dis. 58, 258\u2013269 (2013).","journal-title":"Neurobiol. Dis."},{"key":"1442_CR42","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.biochi.2013.08.009","volume":"98","author":"S Verheijden","year":"2014","unstructured":"Verheijden, S., Beckers, L., De Munter, S., Van Veldhoven, P. P. & Baes, M. Central nervous system pathology in MFP2 deficiency: insights from general and conditional knockout mouse models. Biochimie 98, 119\u2013126 (2014).","journal-title":"Biochimie"},{"key":"1442_CR43","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.nbd.2016.06.012","volume":"94","author":"S De Munter","year":"2016","unstructured":"De Munter, S. et al. Early-onset Purkinje cell dysfunction underlies cerebellar ataxia in peroxisomal multifunctional protein-2 deficiency. Neurobiol. Dis. 94, 157\u2013168 (2016).","journal-title":"Neurobiol. Dis."},{"key":"1442_CR44","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1042\/BST20150127","volume":"43","author":"A Baker","year":"2015","unstructured":"Baker, A. et al. Peroxisomal ABC transporters: functions and mechanism. Biochem Soc. Trans. 43, 959\u2013965 (2015).","journal-title":"Biochem Soc. Trans."},{"key":"1442_CR45","doi-asserted-by":"publisher","first-page":"3565","DOI":"10.1093\/hmg\/ddi384","volume":"14","author":"I Ferrer","year":"2005","unstructured":"Ferrer, I. et al. Inactivation of the peroxisomal ABCD2 transporter in the mouse leads to late-onset ataxia involving mitochondria, Golgi and endoplasmic reticulum damage. Hum. Mol. Genet. 14, 3565\u20133577 (2005).","journal-title":"Hum. Mol. Genet."},{"key":"1442_CR46","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1093\/hmg\/11.5.499","volume":"11","author":"A Pujol","year":"2002","unstructured":"Pujol, A. et al. Late onset neurological phenotype of the X-ALD gene inactivation in mice: a mouse model for adrenomyeloneuropathy. Hum. Mol. Genet. 11, 499\u2013505 (2002).","journal-title":"Hum. Mol. Genet."},{"key":"1442_CR47","doi-asserted-by":"publisher","first-page":"2997","DOI":"10.1093\/hmg\/ddh323","volume":"13","author":"A Pujol","year":"2004","unstructured":"Pujol, A. et al. Functional overlap between ABCD1 (ALD) and ABCD2 (ALDR) transporters: a therapeutic target for X-adrenoleukodystrophy. Hum. Mol. Genet. 13, 2997\u20133006 (2004).","journal-title":"Hum. Mol. Genet."},{"key":"1442_CR48","doi-asserted-by":"publisher","first-page":"9366","DOI":"10.1073\/pnas.94.17.9366","volume":"94","author":"JF Lu","year":"1997","unstructured":"Lu, J. F. et al. A mouse model for X-linked adrenoleukodystrophy. Proc. Natl Acad. Sci. USA 94, 9366\u20139371 (1997).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1442_CR49","doi-asserted-by":"publisher","unstructured":"Duncan, A. L., Song, W. & Sansom, M. S. P. Lipid-dependent regulation of ion channels and G protein-coupled receptors: insights from structures and simulations. Annu. Rev. Pharmacol. Toxicol. https:\/\/doi.org\/10.1146\/annurev-pharmtox-010919-023411 (2019).","DOI":"10.1146\/annurev-pharmtox-010919-023411"},{"key":"1442_CR50","doi-asserted-by":"publisher","first-page":"24698","DOI":"10.1074\/jbc.271.40.24698","volume":"271","author":"CY Fan","year":"1996","unstructured":"Fan, C. Y. et al. Hepatocellular and hepatic peroxisomal alterations in mice with a disrupted peroxisomal fatty acyl-coenzyme A oxidase gene. J. Biol. Chem. 271, 24698\u201324710 (1996).","journal-title":"J. Biol. Chem."},{"key":"1442_CR51","doi-asserted-by":"publisher","first-page":"47232","DOI":"10.1074\/jbc.M306363200","volume":"278","author":"Y Jia","year":"2003","unstructured":"Jia, Y. et al. Overexpression of peroxisome proliferator-activated receptor-alpha (PPARalpha)-regulated genes in liver in the absence of peroxisome proliferation in mice deficient in both L- and D-forms of enoyl-CoA hydratase\/dehydrogenase enzymes of peroxisomal beta-oxidation system. J. Biol. Chem. 278, 47232\u201347239 (2003).","journal-title":"J. Biol. Chem."},{"key":"1442_CR52","doi-asserted-by":"publisher","first-page":"15639","DOI":"10.1074\/jbc.273.25.15639","volume":"273","author":"CY Fan","year":"1998","unstructured":"Fan, C. Y. et al. Steatohepatitis, spontaneous peroxisome proliferation and liver tumors in mice lacking peroxisomal fatty acyl-CoA oxidase. Implications for peroxisome proliferator-activated receptor alpha natural ligand metabolism. J. Biol. Chem. 273, 15639\u201315645 (1998).","journal-title":"J. Biol. Chem."},{"key":"1442_CR53","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1093\/hmg\/ddh107","volume":"13","author":"K Savolainen","year":"2004","unstructured":"Savolainen, K. et al. A mouse model for alpha-methylacyl-CoA racemase deficiency: adjustment of bile acid synthesis and intolerance to dietary methyl-branched lipids. Hum. Mol. Genet. 13, 955\u2013965 (2004).","journal-title":"Hum. Mol. Genet."},{"key":"1442_CR54","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1101\/gad.12.8.1189","volume":"12","author":"U Seedorf","year":"1998","unstructured":"Seedorf, U. et al. Defective peroxisomal catabolism of branched fatty acyl coenzyme A in mice lacking the sterol carrier protein-2\/sterol carrier protein-x gene function. Genes Dev. 12, 1189\u20131201 (1998).","journal-title":"Genes Dev."},{"key":"1442_CR55","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1111\/j.1471-4159.1991.tb02558.x","volume":"56","author":"P Sharp","year":"1991","unstructured":"Sharp, P., Johnson, D. & Poulos, A. Molecular species of phosphatidylcholine containing very long chain fatty acids in human brain: enrichment in X-linked adrenoleukodystrophy brain and diseases of peroxisome biogenesis brain. J. Neurochem. 56, 30\u201337 (1991).","journal-title":"J. Neurochem."},{"key":"1442_CR56","unstructured":"Poulos, A. et al. In Human Genetics, Proceedings of the Seventh International Congress. Berlin, 1986 (eds. Vogel, F. & Sperling, K.) 352\u2013359 (Springer-Verlag, Berlin, 1987)."},{"key":"1442_CR57","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1042\/bj2650763","volume":"265","author":"BS Robinson","year":"1990","unstructured":"Robinson, B. S., Johnson, D. W. & Poulos, A. Unique molecular species of phosphatidylcholine containing very-long-chain (C24-C38) polyenoic fatty acids in rat brain. Biochem. J. 265, 763\u2013767 (1990).","journal-title":"Biochem. J."},{"key":"1442_CR58","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1002\/lipd.12022","volume":"53","author":"K Hama","year":"2018","unstructured":"Hama, K. et al. Profiling and Imaging of phospholipids in brains of Abcd1-deficient mice. Lipids 53, 85\u2013102 (2018).","journal-title":"Lipids"},{"key":"1442_CR59","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.ymgme.2004.09.015","volume":"84","author":"S Kemp","year":"2005","unstructured":"Kemp, S. et al. Elongation of very long-chain fatty acids is enhanced in X-linked adrenoleukodystrophy. Mol. Genet. Metab. 84, 144\u2013151 (2005).","journal-title":"Mol. Genet. Metab."},{"key":"1442_CR60","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1002\/emmm.201000061","volume":"2","author":"R Ofman","year":"2010","unstructured":"Ofman, R. et al. The role of ELOVL1 in very long-chain fatty acid homeostasis and X-linked adrenoleukodystrophy. EMBO Mol. Med. 2, 90\u201397 (2010).","journal-title":"EMBO Mol. Med."},{"key":"1442_CR61","doi-asserted-by":"publisher","first-page":"428","DOI":"10.3389\/fncel.2019.00428","volume":"13","author":"F Deak","year":"2019","unstructured":"Deak, F., Anderson, R. E., Fessler, J. L. & Sherry, D. M. Novel cellular functions of very long chain-fatty acids: insight from ELOVL4 mutations. Front Cell Neurosci. 13, 428 (2019).","journal-title":"Front Cell Neurosci."},{"key":"1442_CR62","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s10545-014-9795-3","volume":"38","author":"AR Malheiro","year":"2015","unstructured":"Malheiro, A. R., da Silva, T. F. & Brites, P. Plasmalogens and fatty alcohols in rhizomelic chondrodysplasia punctata and Sjogren-Larsson syndrome. J. Inherit. Metab. Dis. 38, 111\u2013121 (2015).","journal-title":"J. Inherit. Metab. Dis."},{"key":"1442_CR63","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nature10163","volume":"474","author":"WC Skarnes","year":"2011","unstructured":"Skarnes, W. C. et al. A conditional knockout resource for the genome-wide study of mouse gene function. Nature 474, 337\u2013342 (2011).","journal-title":"Nature"},{"key":"1442_CR64","doi-asserted-by":"publisher","unstructured":"Durkin, M. E., Qian, X., Popescu, N. C. & Lowy, D. R. Isolation of mouse embryo fibroblasts. Bio Protoc. 3, https:\/\/doi.org\/10.21769\/bioprotoc.908 (2013).","DOI":"10.21769\/bioprotoc.908"},{"key":"1442_CR65","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-1-4939-6937-1_1","volume":"1595","author":"A Manner","year":"2017","unstructured":"Manner, A. & Islinger, M. Isolation of peroxisomes from rat liver and cultured hepatoma cells by density gradient centrifugation. Methods Mol. Biol. 1595, 1\u201311 (2017).","journal-title":"Methods Mol. Biol."},{"key":"1442_CR66","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676\u2013682 (2012).","journal-title":"Nat. Methods"},{"key":"1442_CR67","doi-asserted-by":"publisher","first-page":"332","DOI":"10.3389\/fncel.2017.00332","volume":"11","author":"F H\u00f6fflin","year":"2017","unstructured":"H\u00f6fflin, F. et al. Heterogeneity of the axon initial segment in interneurons and pyramidal cells of rodent visual cortex. Front Cell Neurosci. 11, 332 (2017).","journal-title":"Front Cell Neurosci."},{"key":"1442_CR68","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/978-1-4939-6937-1_10","volume":"1595","author":"HD Fahimi","year":"2017","unstructured":"Fahimi, H. D. Cytochemical detection of peroxisomes in light and electron microscopy with 3,3\u2032-diaminobenzidine. Methods Mol. Biol. 1595, 93\u2013100 (2017).","journal-title":"Methods Mol. Biol."},{"key":"1442_CR69","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8923","volume":"6","author":"Y Hua","year":"2015","unstructured":"Hua, Y., Laserstein, P. & Helmstaedter, M. Large-volume en-bloc staining for electron microscopy-based connectomics. Nat. Commun. 6, 7923 (2015).","journal-title":"Nat. Commun."},{"key":"1442_CR70","doi-asserted-by":"publisher","first-page":"10567","DOI":"10.1523\/JNEUROSCI.22-24-10567.2002","volume":"22","author":"K Satzler","year":"2002","unstructured":"Satzler, K. et al. Three-dimensional reconstruction of a calyx of Held and its postsynaptic principal neuron in the medial nucleus of the trapezoid body. J. Neurosci. 22, 10567\u201310579 (2002).","journal-title":"J. Neurosci."},{"key":"1442_CR71","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1159\/000112170","volume":"13","author":"HW Moser","year":"1991","unstructured":"Moser, H. W., Moser, A. B., Naidu, S. & Bergin, A. Clinical aspects of adrenoleukodystrophy and adrenomyeloneuropathy. Dev. Neurosci.-Basel 13, 254\u2013261 (1991).","journal-title":"Dev. Neurosci.-Basel"},{"key":"1442_CR72","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/S0022-2275(20)38802-7","volume":"27","author":"I Bjorkhem","year":"1986","unstructured":"Bjorkhem, I., Sisfontes, L., Bostrom, B., Kase, B. F. & Blomstrand, R. Simple diagnosis of the Zellweger syndrome by gas-liquid chromatography of dimethylacetals. J. Lipid Res. 27, 786\u2013791 (1986).","journal-title":"J. Lipid Res."},{"key":"1442_CR73","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.3748\/wjg.v18.i10.1067","volume":"18","author":"D Haas","year":"2012","unstructured":"Haas, D. et al. Differential diagnosis in patients with suspected bile acid synthesis defects. World J. Gastroenterol. 18, 1067\u20131076 (2012).","journal-title":"World J. Gastroenterol."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-020-01442-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-020-01442-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-020-01442-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T22:10:48Z","timestamp":1670364648000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-020-01442-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,26]]},"references-count":73,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["1442"],"URL":"https:\/\/doi.org\/10.1038\/s42003-020-01442-x","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,26]]},"assertion":[{"value":"4 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 October 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 November 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"713"}}