{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T22:45:42Z","timestamp":1792363542736,"version":"4.4.0"},"reference-count":88,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T00:00:00Z","timestamp":1708300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P 21950-B20"],"award-info":[{"award-number":["P 21950-B20"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P 34723"],"award-info":[{"award-number":["P 34723"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase, HMGCR) is one of the rate-limiting enzymes in the mevalonate pathway required for cholesterol biosynthesis. It is an integral membrane protein of the endoplasmic reticulum (ER) but has occasionally been described in peroxisomes. By co-immunofluorescence microscopy using different HMGCR antibodies, we present evidence for a dual localization of HMGCR in the ER and peroxisomes in differentiated human monocytic THP-1 cells, primary human monocyte-derived macrophages and human primary skin fibroblasts under conditions of low cholesterol and statin treatment. Using density gradient centrifugation and Western blot analysis, we observed a truncated HMGCR variant of 76 kDa in the peroxisomal fractions, while a full-length HMGCR of 96 kDa was contained in fractions of the ER. In contrast to primary human control fibroblasts, peroxisomal HMGCR was not found in fibroblasts from patients suffering from type-1 rhizomelic chondrodysplasia punctata, who lack functional PEX7 and, thus, cannot import peroxisomal matrix proteins harboring a type-2 peroxisomal targeting signal (PTS2). Moreover, in the N\u2013terminal region of the soluble 76 kDa C-terminal catalytic domain, we identified a PTS2-like motif, which was functional in a reporter context. We propose that under sterol-depleted conditions, part of the soluble HMGCR domain, which is released from the ER by proteolytic processing for further turnover, remains sufficiently long in the cytosol for peroxisomal import via a PTS2\/PEX7-dependent mechanism. Altogether, our findings describe a dual localization of HMGCR under combined lipid depletion and statin treatment, adding another puzzle piece to the complex regulation of HMGCR.<\/jats:p>","DOI":"10.3390\/biom14020244","type":"journal-article","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T11:23:57Z","timestamp":1708341837000},"page":"244","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Peroxisomal Localization of a Truncated HMG-CoA Reductase under Low Cholesterol Conditions"],"prefix":"10.3390","volume":"14","author":[{"given":"Jianqiu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Kunze","sequence":"additional","affiliation":[{"name":"Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Villoria-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8455-2069","authenticated-orcid":false,"given":"Isabelle","family":"Weinhofer","sequence":"additional","affiliation":[{"name":"Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0182-2658","authenticated-orcid":false,"given":"Johannes","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/343425a0","article-title":"Regulation of the mevalonate pathway","volume":"343","author":"Goldstein","year":"1990","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1016\/S0022-2275(20)34935-X","article-title":"Post-translational regulation of mevalonate kinase by intermediates of the cholesterol and nonsterol isoprene biosynthetic pathways","volume":"38","author":"Hinson","year":"1997","journal-title":"J. Lipid Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1146\/annurev.biochem.68.1.157","article-title":"Sterols and isoprenoids: Signaling molecules derived from the cholesterol biosynthetic pathway","volume":"68","author":"Edwards","year":"1999","journal-title":"Annu. Rev. Biochem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.ajhg.2023.04.006","article-title":"Bi-allelic variants in hmgcr cause an autosomal-recessive progressive limb-girdle muscular dystrophy","volume":"110","author":"Schwab","year":"2023","journal-title":"Am. J. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7916","DOI":"10.1074\/jbc.271.14.7916","article-title":"Regulation of 3-hydroxy-3-methylglutaryl-coenzyme a reductase degradation by the nonsterol mevalonate metabolite farnesol in vivo","volume":"271","author":"Meigs","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/S0021-9258(17)33712-2","article-title":"Inhibition of 3-hydroxy-3-methylglutaryl coenzyme a reductase activity in hepatoma tissue culture cells by pure cholesterol and several cholesterol derivatives. Evidence supporting two distinct mechanisms.20l","volume":"251","author":"Bell","year":"1976","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7272","DOI":"10.1016\/S0021-9258(18)32171-9","article-title":"Mevalonolactone inhibits the rate of synthesis and enhances the rate of degradation of 3-hydroxy-3-methylglutaryl coenzyme a reductase in rat hepatocytes","volume":"258","author":"Edwards","year":"1983","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1194\/jlr.R800054-JLR200","article-title":"Cholesterol feedback: From schoenheimer\u2019s bottle to scap\u2019s meladl","volume":"50","author":"Brown","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1161\/ATVBAHA.108.179564","article-title":"The ldl receptor","volume":"29","author":"Goldstein","year":"2009","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1126\/science.1059344","article-title":"Structural mechanism for statin inhibition of hmg-coa reductase","volume":"292","author":"Istvan","year":"2001","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrd1112","article-title":"Lovastatin and beyond: The history of the hmg-coa reductase inhibitors","volume":"2","author":"Tobert","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_12","first-page":"554","article-title":"Contrasting effects of lovastatin and cholestyramine on low-density lipoprotein cholesterol and 24-hour urinary mevalonate excretion in patients with heterozygous familial hypercholesterolemia","volume":"114","author":"Pappu","year":"1989","journal-title":"J. Lab. Clin. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0022-2275(20)42221-7","article-title":"Multivalent feedback regulation of hmg coa reductase, a control mechanism coordinating isoprenoid synthesis and cell growth","volume":"21","author":"Brown","year":"1980","journal-title":"J. Lipid Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1073\/pnas.81.6.1674","article-title":"Biogenesis of 3-hydroxy-3-methylglutaryl-coenzyme a reductase, an integral glycoprotein of the endoplasmic reticulum","volume":"81","author":"Brown","year":"1984","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/308613a0","article-title":"Nucleotide sequence of 3-hydroxy-3-methyl-glutaryl coenzyme a reductase, a glycoprotein of endoplasmic reticulum","volume":"308","author":"Chin","year":"1984","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/S0021-9258(18)89764-2","article-title":"Domain structure of 3-hydroxy-3-methylglutaryl coenzyme a reductase, a glycoprotein of the endoplasmic reticulum","volume":"260","author":"Liscum","year":"1985","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"10271","DOI":"10.1016\/S0021-9258(17)39242-6","article-title":"Human 3-hydroxy-3-methylglutaryl coenzyme a reductase. Conserved domains responsible for catalytic activity and sterol-regulated degradation","volume":"260","author":"Luskey","year":"1985","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1083\/jcb.117.5.959","article-title":"Immunological evidence for eight spans in the membrane domain of 3-hydroxy-3-methylglutaryl coenzyme a reductase: Implications for enzyme degradation in the endoplasmic reticulum","volume":"117","author":"Roitelman","year":"1992","journal-title":"J. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Friesen, J.A., and Rodwell, V.W. (2004). The 3-hydroxy-3-methylglutaryl coenzyme-a (hmg-coa) reductases. Genome Biol., 5.","DOI":"10.1186\/gb-2004-5-11-248"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"13797","DOI":"10.1073\/pnas.93.24.13797","article-title":"Proteasome-dependent endoplasmic reticulum-associated protein degradation: An unconventional route to a familiar fate","volume":"93","author":"Werner","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1091\/mbc.e12-07-0564","article-title":"Ancient ubiquitous protein-1 mediates sterol-induced ubiquitination of 3-hydroxy-3-methylglutaryl coa reductase in lipid droplet-associated endoplasmic reticulum membranes","volume":"24","author":"Jo","year":"2013","journal-title":"Mol. Biol. Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/0092-8674(85)90078-9","article-title":"Membrane-bound domain of hmg coa reductase is required for sterol-enhanced degradation of the enzyme","volume":"41","author":"Gil","year":"1985","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"25264","DOI":"10.1016\/S0021-9258(19)74035-6","article-title":"Distinct sterol and nonsterol signals for the regulated degradation of 3-hydroxy-3-methylglutaryl-coa reductase","volume":"267","author":"Roitelman","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13311","DOI":"10.1016\/S0021-9258(18)98840-X","article-title":"Inhibition of degradation of 3-hydroxy-3-methylglutaryl-coenzyme a reductase in vivo by cysteine protease inhibitors","volume":"266","author":"Inoue","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"25630","DOI":"10.1074\/jbc.271.41.25630","article-title":"Degradation of 3-hydroxy-3-methylglutaryl-coa reductase in endoplasmic reticulum membranes is accelerated as a result of increased susceptibility to proteolysis","volume":"271","author":"McGee","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"35840","DOI":"10.1074\/jbc.M004793200","article-title":"The ubiquitin-proteasome pathway mediates the regulated degradation of mammalian 3-hydroxy-3-methylglutaryl-coenzyme a reductase","volume":"275","author":"Ravid","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S1097-2765(02)00822-5","article-title":"Accelerated degradation of hmg coa reductase mediated by binding of insig-1 to its sterol-sensing domain","volume":"11","author":"Sever","year":"2003","journal-title":"Mol. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.semcdb.2017.10.019","article-title":"Underlying mechanisms for sterol-induced ubiquitination and er-associated degradation of hmg coa reductase","volume":"81","author":"Johnson","year":"2018","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19288","DOI":"10.1074\/jbc.M110.134213","article-title":"Sterol-induced dislocation of 3-hydroxy-3-methylglutaryl coenzyme a reductase from endoplasmic reticulum membranes into the cytosol through a subcellular compartment resembling lipid droplets","volume":"285","author":"Hartman","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1073\/pnas.82.3.770","article-title":"3-hydroxy-3-methylglutaryl-coenzyme a reductase is present in peroxisomes in normal rat liver cells","volume":"82","author":"Keller","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/S0022-2275(20)38491-1","article-title":"Localization of 3-hydroxy-3-methylglutaryl coa reductase and 3-hydroxy-3-methylglutaryl coa synthase in the rat liver and intestine is affected by cholestyramine and mevinolin","volume":"29","author":"Li","year":"1988","journal-title":"J. Lipid Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4850","DOI":"10.1046\/j.0014-2956.2001.02409.x","article-title":"Purification of brain peroxisomes and localization of 3-hydroxy-3-methylglutaryl coenzyme a reductase","volume":"268","author":"Kovacs","year":"2001","journal-title":"Eur. J. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.bbalip.2010.01.001","article-title":"Peroxisomes, lipid metabolism and lipotoxicity","volume":"1801","author":"Wanders","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s00418-012-0941-4","article-title":"The peroxisome: An update on mysteries","volume":"137","author":"Islinger","year":"2012","journal-title":"Histochem. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/j.1399-0004.2004.00329.x","article-title":"Peroxisomal disorders i: Biochemistry and genetics of peroxisome biogenesis disorders","volume":"67","author":"Wanders","year":"2005","journal-title":"Clin. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1016\/j.bbamcr.2006.08.010","article-title":"Peroxisomal disorders: The single peroxisomal enzyme deficiencies","volume":"1763","author":"Wanders","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_37","first-page":"111","article-title":"Peroxisome biogenesis disorders","volume":"1","author":"Argyriou","year":"2016","journal-title":"Transl. Sci. Rare Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.bbamcr.2015.11.015","article-title":"Human disorders of peroxisome metabolism and biogenesis","volume":"1863","author":"Waterham","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1152\/physrev.00051.2021","article-title":"The physiological functions of human peroxisomes","volume":"103","author":"Wanders","year":"2023","journal-title":"Physiol. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1146\/annurev.biochem.74.082803.133329","article-title":"Biochemistry of mammalian peroxisomes revisited","volume":"75","author":"Wanders","year":"2006","journal-title":"Annu. Rev. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.bbamcr.2015.12.005","article-title":"Peroxisomes in brain development and function","volume":"1863","author":"Berger","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Dorninger, F., Werner, E.R., Berger, J., and Watschinger, K. (2022). Regulation of plasmalogen metabolism and traffic in mammals: The fog begins to lift. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.946393"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Dorninger, F., Forss-Petter, S., Wimmer, I., and Berger, J. (2020). Plasmalogens, platelet-activating factor and beyond\u2014Ether lipids in signaling and neurodegeneration. Neurobiol. Dis., 145.","DOI":"10.1016\/j.nbd.2020.105061"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Weinhofer, I., Buda, A., Kunze, M., Palfi, Z., Traunfellner, M., Hesse, S., Villoria-Gonzalez, A., Hofmann, J., Hametner, S., and Regelsberger, G. (2022). Peroxisomal very long-chain fatty acid transport is targeted by herpesviruses and the antiviral host response. Commun. Biol., 5.","DOI":"10.1038\/s42003-022-03867-y"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.tcb.2021.09.010","article-title":"Emerging roles of peroxisomes in viral infections","volume":"32","author":"Ferreira","year":"2022","journal-title":"Trends Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1083\/jcb.103.3.875","article-title":"3-hydroxy-3-methylglutaryl coenzyme a reductase localization in rat liver peroxisomes and microsomes of control and cholestyramine-treated animals: Quantitative biochemical and immunoelectron microscopical analyses","volume":"103","author":"Keller","year":"1986","journal-title":"J. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/0006-291X(87)90959-4","article-title":"Diurnal variation of hmg-coa reductase activity in rat liver peroxisomes","volume":"148","author":"Rusnak","year":"1987","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5560","DOI":"10.1016\/S0021-9258(18)42802-5","article-title":"Mevalonate kinase is localized in rat liver peroxisomes","volume":"267","author":"Stamellos","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"12825","DOI":"10.1016\/S0021-9258(18)31462-5","article-title":"Subcellular localization of squalene synthase in rat hepatic cells. Biochemical and immunochemical evidence","volume":"268","author":"Stamellos","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"14165","DOI":"10.1016\/S0021-9258(17)36769-8","article-title":"Farnesyl-diphosphate synthase is localized in peroxisomes","volume":"269","author":"Krisans","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.biochi.2013.10.019","article-title":"Cholesterol biosynthesis and er stress in peroxisome deficiency","volume":"98","author":"Faust","year":"2014","journal-title":"Biochimie"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s00418-006-0254-6","article-title":"Localization of the pre-squalene segment of the isoprenoid biosynthetic pathway in mammalian peroxisomes","volume":"127","author":"Kovacs","year":"2007","journal-title":"Histochem. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0163-7827(02)00002-4","article-title":"Central role of peroxisomes in isoprenoid biosynthesis","volume":"41","author":"Kovacs","year":"2002","journal-title":"Prog. Lipid Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/S0022-2275(20)30191-7","article-title":"Absence of functional peroxisomes does not lead to deficiency of enzymes involved in cholesterol biosynthesis","volume":"43","author":"Hogenboom","year":"2002","journal-title":"J. Lipid Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/S1096-7192(03)00143-4","article-title":"Cholesterol biosynthesis is not defective in peroxisome biogenesis defective fibroblasts","volume":"80","author":"Hogenboom","year":"2003","journal-title":"Mol. Genet. Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1194\/jlr.M300373-JLR200","article-title":"Phosphomevalonate kinase is a cytosolic protein in humans","volume":"45","author":"Hogenboom","year":"2004","journal-title":"J. Lipid Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1242\/jcs.00910","article-title":"Mevalonate kinase is a cytosolic enzyme in humans","volume":"117","author":"Hogenboom","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.ymgme.2003.12.001","article-title":"Human mevalonate pyrophosphate decarboxylase is localized in the cytosol","volume":"81","author":"Hogenboom","year":"2004","journal-title":"Mol. Genet. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.bbalip.2012.02.011","article-title":"Peroxisome deficiency-induced er stress and srebp-2 pathway activation in the liver of newborn pex2 knock-out mice","volume":"1821","author":"Kovacs","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1016\/S0022-2275(20)32165-9","article-title":"Analysis of isoprenoid biosynthesis in peroxisomal-deficient pex2 cho cell lines","volume":"39","author":"Aboushadi","year":"1998","journal-title":"J. Lipid Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/MCB.24.1.1-13.2004","article-title":"Disturbed cholesterol homeostasis in a peroxisome-deficient pex2 knockout mouse model","volume":"24","author":"Kovacs","year":"2004","journal-title":"Mol Cell Biol"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Charles, K.N., Shackelford, J.E., Faust, P.L., Fliesler, S.J., Stangl, H., and Kovacs, W.J. (2020). Functional peroxisomes are essential for efficient cholesterol sensing and synthesis. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.560266"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.cell.2015.02.019","article-title":"Cholesterol transport through lysosome-peroxisome membrane contacts","volume":"161","author":"Chu","year":"2015","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e103499","DOI":"10.15252\/embj.2019103499","article-title":"Insufficiency of ciliary cholesterol in hereditary zellweger syndrome","volume":"39","author":"Miyamoto","year":"2020","journal-title":"EMBO J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.bbrc.2006.04.078","article-title":"Peroxisomal cholesterol biosynthesis and smith-lemli-opitz syndrome","volume":"345","author":"Weinhofer","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Buda, A., Forss-Petter, S., Hua, R., Jaspers, Y., Lassnig, M., Waidhofer-Sollner, P., Kemp, S., Kim, P., Weinhofer, I., and Berger, J. (2023). Abcd1 transporter deficiency results in altered cholesterol homeostasis. Biomolecules, 13.","DOI":"10.3390\/biom13091333"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5512","DOI":"10.1016\/j.febslet.2005.09.014","article-title":"X-linked adrenoleukodystrophy mice demonstrate abnormalities in cholesterol metabolism","volume":"579","author":"Weinhofer","year":"2005","journal-title":"FEBS Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0022-2275(20)41539-1","article-title":"Hmg-coa reductase inhibitors perturb fatty acid metabolism and induce peroxisomes in keratinocytes","volume":"33","author":"Williams","year":"1992","journal-title":"J. Lipid Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.tibs.2018.01.001","article-title":"Mind the organelle gap\u2014Peroxisome contact sites in disease","volume":"43","author":"Castro","year":"2018","journal-title":"Trends Biochem. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1083\/jcb.201607055","article-title":"Acbd5 and vapb mediate membrane associations between peroxisomes and the er","volume":"216","author":"Costello","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1083\/jcb.201608128","article-title":"Vaps and acbd5 tether peroxisomes to the er for peroxisome maintenance and lipid homeostasis","volume":"216","author":"Hua","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1083\/jcb.201902061","article-title":"Spastin tethers lipid droplets to peroxisomes and directs fatty acid trafficking through escrt-iii","volume":"218","author":"Chang","year":"2019","journal-title":"J. Cell Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"127","DOI":"10.37349\/ent.2021.00011","article-title":"Peroxisomes in intracellular cholesterol transport: From basic physiology to brain pathology","volume":"1","author":"Xiao","year":"2021","journal-title":"Explor. Neuroprot. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.bbalip.2014.11.005","article-title":"Homeostasis of phospholipids\u2014The level of phosphatidylethanolamine tightly adapts to changes in ethanolamine plasmalogens","volume":"1851","author":"Dorninger","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/humu.10124","article-title":"Mutation analysis of pex7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype","volume":"20","author":"Braverman","year":"2002","journal-title":"Hum. Mutat."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Villoria-Gonzalez, A., Zierfuss, B., Parzer, P., Heubock, E., Zujovic, V., Waidhofer-Sollner, P., Ponleitner, M., Rommer, P., Gopfert, J., and Forss-Petter, S. (2023). Efficacy of hdac inhibitors in driving peroxisomal beta-oxidation and immune responses in human macrophages: Implications for neuroinflammatory disorders. Biomolecules, 13.","DOI":"10.3390\/biom13121696"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"9734","DOI":"10.1074\/jbc.273.16.9734","article-title":"Ubiquitination is required for the retro-translocation of a short-lived luminal endoplasmic reticulum glycoprotein to the cytosol for degradation by the proteasome","volume":"273","author":"Weninger","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"19269","DOI":"10.1074\/jbc.M112.445445","article-title":"Impaired very long-chain acyl-coa beta-oxidation in human x-linked adrenoleukodystrophy fibroblasts is a direct consequence of abcd1 transporter dysfunction","volume":"288","author":"Wiesinger","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"45048","DOI":"10.1074\/jbc.M111.301853","article-title":"Structural requirements for interaction of peroxisomal targeting signal 2 and its receptor pex7","volume":"286","author":"Kunze","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1073\/pnas.81.3.894","article-title":"Divergence in cholesterol biosynthetic rates and 3-hydroxy-3-methylglutaryl-coa reductase activity as a consequence of granulocyte versus monocyte-macrophage differentiation in hl-60 cells","volume":"81","author":"Yachnin","year":"1984","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1194\/jlr.R200010-JLR200","article-title":"A second gene for peroxisomal hmg-coa reductase? A genomic reassessment","volume":"43","author":"Breitling","year":"2002","journal-title":"J. Lipid Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"24579","DOI":"10.1074\/jbc.272.39.24579","article-title":"Characterization of ut2 cells. The induction of peroxisomal 3-hydroxy-3-methylglutaryl-coenzyme a reductase","volume":"272","author":"Engfelt","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"39308","DOI":"10.1074\/jbc.M608999200","article-title":"Sterol-regulated degradation of insig-1 mediated by the membrane-bound ubiquitin ligase gp78","volume":"281","author":"Lee","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Kunze, M. (2020). The type-2 peroxisomal targeting signal. Biochim. Et Biophys. Acta. Mol. Cell Res., 1867.","DOI":"10.1016\/j.bbamcr.2019.118609"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jmb.2004.05.064","article-title":"A new definition for the consensus sequence of the peroxisome targeting signal type 2","volume":"341","author":"Petriv","year":"2004","journal-title":"J. Mol. Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"7165","DOI":"10.1073\/pnas.80.23.7165","article-title":"3-hydroxy-3-methylglutaryl-coa reductase: A transmembrane glycoprotein of the endoplasmic reticulum with n-linked \u201chigh-mannose\u201d oligosaccharides","volume":"80","author":"Liscum","year":"1983","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1093\/hmg\/ddu448","article-title":"A novel bile acid biosynthesis defect due to a deficiency of peroxisomal abcd3","volume":"24","author":"Ferdinandusse","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/S0021-9258(17)42242-3","article-title":"Mevalonate kinase is predominantly localized in peroxisomes and is defective in patients with peroxisome deficiency disorders","volume":"269","author":"Biardi","year":"1994","journal-title":"J. Biol. Chem."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/2\/244\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:02:27Z","timestamp":1760104947000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/2\/244"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,19]]},"references-count":88,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["biom14020244"],"URL":"https:\/\/doi.org\/10.3390\/biom14020244","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,19]]}}}