Mice with a deficiency in Peroxisomal Membrane Protein 4 (PXMP4) display mild changes in hepatic lipid metabolism.
Animals
Bile Acids and Salts
/ metabolism
CRISPR-Cas Systems
Diet
/ methods
Fatty Acids
/ metabolism
Fatty Acids, Unsaturated
/ metabolism
Female
Fenofibrate
/ administration & dosage
Gene Editing
/ methods
Gene Knockout Techniques
/ methods
Liver
/ metabolism
Male
Membrane Proteins
/ genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Oxidation-Reduction
/ drug effects
PPAR alpha
/ metabolism
Peroxisomes
/ drug effects
Phytanic Acid
/ metabolism
Phytol
/ administration & dosage
Signal Transduction
/ genetics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
15 02 2022
15 02 2022
Historique:
received:
28
10
2020
accepted:
31
01
2022
entrez:
16
2
2022
pubmed:
17
2
2022
medline:
15
3
2022
Statut:
epublish
Résumé
Peroxisomes play an important role in the metabolism of a variety of biomolecules, including lipids and bile acids. Peroxisomal Membrane Protein 4 (PXMP4) is a ubiquitously expressed peroxisomal membrane protein that is transcriptionally regulated by peroxisome proliferator-activated receptor α (PPARα), but its function is still unknown. To investigate the physiological function of PXMP4, we generated a Pxmp4 knockout (Pxmp4
Identifiants
pubmed: 35169201
doi: 10.1038/s41598-022-06479-y
pii: 10.1038/s41598-022-06479-y
pmc: PMC8847483
doi:
Substances chimiques
Bile Acids and Salts
0
Fatty Acids
0
Fatty Acids, Unsaturated
0
Membrane Proteins
0
PPAR alpha
0
Ppara protein, mouse
0
Pxmp4 protein, mouse
0
Phytanic Acid
14721-66-5
Phytol
150-86-7
pristanic acid
5FMQ2908AP
Fenofibrate
U202363UOS
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2512Informations de copyright
© 2022. The Author(s).
Références
Wanders, R. J. A. Biochimie metabolic functions of peroxisomes in health and disease. Biochimie 98, 36–44 (2014).
pubmed: 24012550
doi: 10.1016/j.biochi.2013.08.022
Islinger, M., Voelkl, A., Fahimi, H. D. & Schrader, M. The peroxisome: An update on mysteries 20. Histochem. Cell Biol. 150, 443–471 (2018).
pubmed: 30219925
pmcid: 6182659
doi: 10.1007/s00418-018-1722-5
Braverman, N. E., D’Agostino, M. D. & Maclean, G. E. Peroxisome biogenesis disorders: Biological, clinical and pathophysiological perspectives. Dev. Disabil. Res. Rev. 17, 187–196 (2013).
pubmed: 23798008
doi: 10.1002/ddrr.1113
Waterham, H. R., Ferdinandusse, S. & Wanders, R. J. A. Human disorders of peroxisome metabolism and biogenesis. Biochim. Biophys. Acta. 2016, 922–933 (1863).
Baes, M. & Van Veldhoven, P. P. Mouse models for peroxisome biogenesis defects and β-oxidation enzyme deficiencies. Biochim. Biophys. Acta Mol. Basis Dis. 2012, 1489–1500 (1822).
Baes, M. & Van Veldhoven, P. P. Hepatic dysfunction in peroxisomal disorders. Biochim. Biophys. Acta Mol. Cell Res. 2016, 956–970 (1863).
Ferdinandusse, S. et al. Ataxia with loss of Purkinje cells in a mouse model for Refsum disease. Proc. Natl. Acad. Sci. 105, 17712–17717 (2008).
pubmed: 19004801
pmcid: 2584743
doi: 10.1073/pnas.0806066105
Vapola, M. H. et al. Peroxisomal membrane channel Pxmp2 in the mammary fat pad is essential for stromal lipid homeostasis and for development of mammary gland epithelium in mice. Dev. Biol. 391, 66–80 (2014).
pubmed: 24726525
doi: 10.1016/j.ydbio.2014.03.022
Selkälä, E. M. et al. Metabolic adaptation allows Amacr-deficient mice to remain symptom-free despite low levels of mature bile acids. BBA Mol. Cell Biol. Lipids 2013, 1335–1343 (1831).
Ferdinandusse, S. et al. A novel bile acid biosynthesis defect due to a deficiency of peroxisomal ABCD3. Hum. Mol. Genet. 24, 361–370 (2015).
pubmed: 25168382
doi: 10.1093/hmg/ddu448
Issemann, I. & Green, S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347, 645–650 (1990).
pubmed: 2129546
doi: 10.1038/347645a0
Forman, B. M., Chen, J. & Evans, R. M. The peroxisome proliferator-activated receptors: Ligands and activators. Ann. N. Y. Acad. Sci. 804, 266–275 (1996).
pubmed: 8993549
doi: 10.1111/j.1749-6632.1996.tb18621.x
Lodhi, I. J. & Semenkovich, C. F. Review peroxisomes: A nexus for lipid metabolism and cellular signaling. Cell Metab. 19, 380–392 (2014).
pubmed: 24508507
pmcid: 3951609
doi: 10.1016/j.cmet.2014.01.002
Wanders, R. J. A., Ferdinandusse, S., Brites, P. & Kemp, S. Peroxisomes, lipid metabolism and lipotoxicity. Biochim. Biophys. Acta 2010, 272–280 (1801).
Berger, J. P., Akiyama, T. E. & Meinke, P. T. PPARs: Therapeutic targets for metabolic disease. Trends Pharmacol. Sci. 26, 244–251 (2005).
pubmed: 15860371
doi: 10.1016/j.tips.2005.03.003
Gross, B., Pawlak, M., Lefebvre, P. & Staels, B. PPARs in obesity-induced T2DM, dyslipidaemia and NAFLD. Nat. Rev. Endocrinol. 13, 36–49 (2017).
pubmed: 27636730
doi: 10.1038/nrendo.2016.135
Braissant, O., Foufelle, F., Scotto, C., Dauça, M. & Wahli, W. Differential expression of peroxisome proliferator-activated receptors (PPARs): Tissue distribution of PPAR-α, -β, and -γ in the adult rat. Endocrinology 137, 354–366 (1996).
pubmed: 8536636
doi: 10.1210/endo.137.1.8536636
Kersten, S. et al. Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J. Clin. Investig. 103, 1489–1498 (1999).
pubmed: 10359558
pmcid: 408372
doi: 10.1172/JCI6223
Leone, T. C., Weinheimer, C. J. & Kelly, D. P. A critical role for the peroxisome proliferator-activated receptor α (PPARα) in the cellular fasting response: The PPARα-null mouse as a model of fatty acid oxidation disorders. Proc. Natl. Acad. Sci. U. S. A. 96, 7473–7478 (1999).
pubmed: 10377439
pmcid: 22110
doi: 10.1073/pnas.96.13.7473
Grabacka, M., Pierzchalska, M., Dean, M. & Reiss, K. Regulation of ketone body metabolism and the role of PPARalpha. Int. J. Mol. Sci. 17, 2093 (2016).
pmcid: 5187893
doi: 10.3390/ijms17122093
Patsouris, D. et al. PPARalpha governs glycerol metabolism. J. Clin. Investig. 114, 94–103 (2004).
pubmed: 15232616
pmcid: 437964
doi: 10.1172/JCI200420468
Iroz, A. et al. A specific ChREBP and PPARα cross-talk is required for the glucose-mediated FGF21 response. Cell Rep. 21, 403–416 (2017).
pubmed: 29020627
pmcid: 5643524
doi: 10.1016/j.celrep.2017.09.065
Rakhshandehroo, M., Hooiveld, G., Muller, M. & Kersten, S. Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human. PLoS One 4, e6796 (2009).
pubmed: 19710929
pmcid: 2729378
doi: 10.1371/journal.pone.0006796
Mattijssen, F. et al. Hypoxia-inducible lipid droplet-associated (HILPDA) is a novel peroxisome proliferator-activated receptor (PPAR) target involved in hepatic triglyceride secretion. J. Biol. Chem. 289, 19279–19293 (2014).
pubmed: 24876382
pmcid: 4094041
doi: 10.1074/jbc.M114.570044
Rosen, M. B. et al. Gene profiling in the livers of wild-type and PPARα-null mice exposed to perfluorooctanoic acid. Toxicol. Pathol. 36, 592–607 (2008).
pubmed: 18467677
doi: 10.1177/0192623308318208
Hruz, T. et al. Genevestigator v3: A reference expression database for the meta-analysis of transcriptomes. Adv. Bioinform. 2008, 420747 (2008).
Reguenga, C. et al. Identification of a 24 kDa intrinsic membrane protein from mammalian peroxisomes. Biochim. Biophys. Acta 1445, 337–341 (1999).
pubmed: 10366717
doi: 10.1016/S0167-4781(99)00061-5
Cosmic, PXMP4 Gene—Somatic Mutations in Cancer (n.d.). https://cancer.sanger.ac.uk/cosmic . Accessed on 2021.
Saghafinia, S., Mina, M., Riggi, N., Hanahan, D. & Ciriello, G. Pan-cancer landscape of aberrant DNA methylation across human tumors. Cell Rep. 25, 1066-1080.e8 (2018).
pubmed: 30355485
doi: 10.1016/j.celrep.2018.09.082
Atshaves, B. P. et al. Effect of SCP-x gene ablation on branched-chain fatty acid metabolism. Am. J. Physiol. Gastrointest. Liver Physiol. 292, G939–G951 (2007).
pubmed: 17068117
doi: 10.1152/ajpgi.00308.2006
Selkälä, E. M. et al. Phytol is lethal for Amacr-deficient mice. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1851, 1394–1405 (2015).
doi: 10.1016/j.bbalip.2015.07.008
Ferdinandusse, S., Denis, S., Faust, P. L. & Wanders, R. J. A. Bile acids: The role of peroxisomes. J. Lipid Res. 50, 2139–2147 (2009).
pubmed: 19357427
pmcid: 2759819
doi: 10.1194/jlr.R900009-JLR200
Atshaves, B. P. et al. Effect of branched-chain fatty acid on lipid dynamics in mice lacking liver fatty acid binding protein gene. Am. J. Physiol. Cell Physiol. 288, 543–558 (2005).
doi: 10.1152/ajpcell.00359.2004
Gloerich, J. et al. A phytol-enriched diet induces changes in fatty acid metabolism in mice both via PPARalpha-dependent and -independent pathways. J. Lipid Res. 46, 716–726 (2005).
pubmed: 15654129
doi: 10.1194/jlr.M400337-JLR200
Mackie, J. et al. Phytol-induced hepatotoxicity in mice. Toxicol. Pathol. 37, 201–208 (2009).
pubmed: 19188468
pmcid: 2838495
doi: 10.1177/0192623308330789
Brites, P. et al. Impaired neuronal migration and endochondral ossification in Pex7 knockout mice: A model for rhizomelic chondrodysplasia punctata. Hum. Mol. Genet. 12, 2255–2267 (2003).
pubmed: 12915479
doi: 10.1093/hmg/ddg236
Landrock, D. et al. Effect of Fabp1/Scp-2/Scp-x ablation on whole body and hepatic phenotype of phytol-fed male mice. Lipids 52, 385–397 (2017).
pubmed: 28382456
pmcid: 5500168
doi: 10.1007/s11745-017-4249-y
Mezzar, S. et al. Phytol-induced pathology in 2-hydroxyacyl-CoA lyase (HACL1) deficient mice Evidence for a second non-HACL1-related lyase. Biochim. Biophys. Acta. Mol. Cell Biol. Lipids 2017, 972–990 (1862).
Facciotti, F. et al. Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus. Nat. Immunol. 13, 474–480 (2012).
pubmed: 22426352
doi: 10.1038/ni.2245
Fletcher, J. M. et al. Congenic analysis of the NKT cell control gene Nkt2 implicates the peroxisomal protein Pxmp4. J. Immunol. 181, 3400–3412 (2008).
pubmed: 18714012
doi: 10.4049/jimmunol.181.5.3400
Dahabieh, M. S. et al. Peroxisomes and cancer: The role of a metabolic specialist in a disease of aberrant metabolism. Biochim. Biophys. Acta Rev. Cancer 2018, 103–121 (1870).
Wu, M. & Ho, S.-M. PMP24, a gene identified by MSRF, undergoes DNA hypermethylation-associated gene silencing during cancer progression in an LNCaP model. Oncogene 23, 250–259 (2004).
pubmed: 14712230
doi: 10.1038/sj.onc.1207076
Zhang, X. et al. Methylation of a single intronic CpG mediates expression silencing of the PMP24 gene in prostate cancer. Prostate 70, 765–776 (2010).
pubmed: 20054818
pmcid: 2857536
doi: 10.1002/pros.21109
Grabowska, M. M. et al. Mouse models of prostate cancer: Picking the best model for the question. Cancer Metastasis Rev. 33, 377–397 (2014).
pubmed: 24452759
pmcid: 4108581
doi: 10.1007/s10555-013-9487-8
Zomer, A. W. M. et al. Pristanic acid and phytanic acid: Naturally occurring ligands for the nuclear receptor peroxisome proliferator-activated receptor. J. Lipid Res. 41, 1801–1807 (2000).
pubmed: 11060349
doi: 10.1016/S0022-2275(20)31973-8
Berger, J. et al. The four murine peroxisomal ABC-transporter genes differ in constitutive, inducible and developmental expression. Eur. J. Biochem. 265, 719–727 (1999).
pubmed: 10504404
doi: 10.1046/j.1432-1327.1999.00772.x
Fourcade, S. et al. Fibrate induction of the adrenoleukodystrophy-related gene (ABCD2): Promoter analysis and role of the peroxisome proliferator-activated receptor PPARalpha. Eur. J. Biochem. 268, 3490–3500 (2001).
pubmed: 11422379
doi: 10.1046/j.1432-1327.2001.02249.x
Li, T. & Chiang, J. Y. L. Regulation of bile acid and cholesterol metabolism by PPARs. PPAR Res. 2009, 1–15 (2009).
doi: 10.1155/2009/501739
Post, S. M. et al. Fibrates suppress bile acid synthesis via peroxisome proliferator-activated receptor-α-mediated downregulation of cholesterol 7α-hydroxylase and sterol 27-hydroxylase expression. Arterioscler. Thromb. Vasc. Biol. 21, 1840–1845 (2001).
pubmed: 11701475
doi: 10.1161/hq1101.098228
Zhang, Y., Lickteig, A. J., Csanaky, I. L. & Klaassen, C. D. Clofibrate decreases bile acids in livers of male mice by increasing biliary bile acid excretion in a PPARα- dependent manner. Toxicol. Sci. 160, 351–360 (2017).
pubmed: 28973556
pmcid: 5837458
doi: 10.1093/toxsci/kfx191
Kok, T. et al. Peroxisome proliferator-activated receptor α (PPARα)-mediated regulation of multidrug resistance 2 (Mdr2) expression and function in mice. Biochem. J. 369, 539–547 (2003).
pubmed: 12381268
pmcid: 1223107
doi: 10.1042/bj20020981
Oosterveer, M. H. et al. Fenofibrate simultaneously induces hepatic fatty acid oxidation, synthesis, and elongation in mice. J. Biol. Chem. 284, 34036–34044 (2009).
pubmed: 19801551
pmcid: 2797174
doi: 10.1074/jbc.M109.051052
Solaas, K. et al. Differential regulation of cytosolic and peroxisomal bile acid amidation by PPARα activation favors the formation of unconjugated bile acids. J. Lipid Res. 45, 1051–1060 (2004).
pubmed: 15026425
doi: 10.1194/jlr.M300291-JLR200
Wanders, R. J. A., Komen, J. & Ferdinandusse, S. Phytanic acid metabolism in health and disease. BBA Mol. Cell Biol. Lipids 2011, 498–507 (1811).
Gloerich, J. et al. Metabolism of phytol to phytanic acid in the mouse, and the role of PPARalpha in its regulation. J. Lipid Res. 48, 77–85 (2007).
pubmed: 17015885
doi: 10.1194/jlr.M600050-JLR200
Dean, J. M. & Lodhi, I. J. Structural and functional roles of ether lipids. Protein Cell 9, 196–206 (2018).
pubmed: 28523433
doi: 10.1007/s13238-017-0423-5
van Ael, E. Studies of the Mammalian Peroxisomal Membrane Protein PMP34 (Leuven, 2008).
Schmitz, W., Fingerhut, R. & Conzelmann, E. Purification and properties of an α-methylacyl-CoA racemase from rat liver. Eur. J. Biochem. 222, 313–323 (1994).
pubmed: 8020470
doi: 10.1111/j.1432-1033.1994.tb18870.x
Ferdinandusse, S. et al. Subcellular localization and physiological role of alpha-methylacyl-CoA racemase. J. Lipid Res. 41, 1890–1896 (2000).
pubmed: 11060359
doi: 10.1016/S0022-2275(20)31983-0
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, 955–965 (2004).
pubmed: 15016763
doi: 10.1093/hmg/ddh107
Karczewski, K. J. et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581, 434–443 (2020).
pubmed: 32461654
pmcid: 7334197
doi: 10.1038/s41586-020-2308-7
Lek, M. et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature 536, 285–291 (2016).
pubmed: 27535533
pmcid: 5018207
doi: 10.1038/nature19057
Žárský, V. & Doležal, P. Evolution of the Tim17 protein family. Biol. Direct. 11, 1–13 (2016).
doi: 10.1186/s13062-016-0157-y
Exil, V. J. et al. Stressed-induced TMEM135 protein is part of a conserved genetic network involved in fat storage and longevity regulation in Caenorhabditis elegans. PLoS ONE 5, e14228 (2010).
pubmed: 21151927
pmcid: 2997067
doi: 10.1371/journal.pone.0014228
Kersten, S. & Stienstra, R. The role and regulation of the peroxisome proliferator activated receptor alpha in human liver. Biochimie 136, 75–84 (2017).
pubmed: 28077274
doi: 10.1016/j.biochi.2016.12.019
McMullen, P. D. et al. A map of the PPARα transcription regulatory network for primary human hepatocytes. Chem. Biol. Interact. 209, 14–24 (2014).
pubmed: 24269660
doi: 10.1016/j.cbi.2013.11.006
Wang, H. et al. One-step generation of mice carrying mutations in multiple genes by CRISPR/cas-mediated genome engineering. Cell 153, 910–918 (2013).
pubmed: 23643243
pmcid: 3969854
doi: 10.1016/j.cell.2013.04.025
van de Peppel, I. P. et al. Efficient reabsorption of transintestinally excreted cholesterol is a strong determinant for cholesterol disposal in mice. J. Lipid Res. 60(9), 1562–1572 (2019).
pubmed: 31324653
pmcid: 6718438
doi: 10.1194/jlr.M094607
de Boer, P. et al. Large-scale electron microscopy database for human type 1 diabetes. Nat. Commun. 11, 1–9 (2020).
Kuipers, J. & Giepmans, B. N. G. Neodymium as an alternative contrast for uranium in electron microscopy. Histochem. Cell Biol. 153, 271–277 (2020).
pubmed: 32008069
pmcid: 7160090
doi: 10.1007/s00418-020-01846-0
Herzog, K. et al. Lipidomic analysis of fibroblasts from Zellweger spectrum disorder patients identifies disease-specific phospholipid ratios. J. Lipid Res. 57, 1447–1454 (2016).
pubmed: 27284103
pmcid: 4959860
doi: 10.1194/jlr.M067470
Chambers, M. C. et al. A cross-platform toolkit for mass spectrometry and proteomics. Nat. Biotechnol. 30, 918–920 (2012).
pubmed: 23051804
pmcid: 3471674
doi: 10.1038/nbt.2377
Wolters, J. C. et al. Translational targeted proteomics profiling of mitochondrial energy metabolic pathways in mouse and human samples. J. Proteome Res. 15, 3204–3213 (2016).
pubmed: 27447838
doi: 10.1021/acs.jproteome.6b00419
MacLean, B. et al. Skyline: An open source document editor for creating and analyzing targeted proteomics experiments. Bioinformatics 26, 966–968 (2010).
pubmed: 20147306
pmcid: 2844992
doi: 10.1093/bioinformatics/btq054
Vreken, P. et al. Rapid stable isotope dilution analysis of very-long-chain fatty acids, pristanic acid and phytanic acid using gas chromatography-electron impact mass spectrometry. J. Chromatogr. B. Biomed. Sci. Appl. 713, 281–287 (1998).
pubmed: 9746242
doi: 10.1016/S0378-4347(98)00186-8