Peroxisomal biogenesis is genetically and biochemically linked to carbohydrate metabolism in Drosophila and mouse

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dc.citation.articleNumbere1006825en_US
dc.citation.issueNumber6en_US
dc.citation.journalTitlePLoS Geneticsen_US
dc.citation.volumeNumber13en_US
dc.contributor.authorWangler, Michael F.en_US
dc.contributor.authorChao, Yu-Hsinen_US
dc.contributor.authorBayat, Vafaen_US
dc.contributor.authorGiagtzoglou, Nikolaosen_US
dc.contributor.authorShinde, Abhijit Babajien_US
dc.contributor.authorPutluri, Nagireddyen_US
dc.contributor.authorCoarfa, Cristianen_US
dc.contributor.authorDonti, Tarakaen_US
dc.contributor.authorGraham, Brett H.en_US
dc.contributor.authorFaust, Joseph E.en_US
dc.contributor.authorMcNew, James A.en_US
dc.contributor.authorMoser, Annen_US
dc.contributor.authorSardiello, Marcoen_US
dc.contributor.authorBaes, Myriamen_US
dc.contributor.authorBellen, Hugo J.en_US
dc.date.accessioned2017-07-31T18:12:32Zen_US
dc.date.available2017-07-31T18:12:32Zen_US
dc.date.issued2017en_US
dc.description.abstractPeroxisome biogenesis disorders (PBD) are a group of multi-system human diseases due to mutations in the PEX genes that are responsible for peroxisome assembly and function. These disorders lead to global defects in peroxisomal function and result in severe brain, liver, bone and kidney disease. In order to study their pathogenesis we undertook a systematic genetic and biochemical study of Drosophila pex16 and pex2 mutants. These mutants are short-lived with defects in locomotion and activity. Moreover these mutants exhibit severe morphologic and functional peroxisomal defects. Using metabolomics we uncovered defects in multiple biochemical pathways including defects outside the canonical specialized lipid pathways performed by peroxisomal enzymes. These included unanticipated changes in metabolites in glycolysis, glycogen metabolism, and the pentose phosphate pathway, carbohydrate metabolic pathways that do not utilize known peroxisomal enzymes. In addition, mutant flies are starvation sensitive and are very sensitive to glucose deprivation exhibiting dramatic shortening of lifespan and hyperactivity on low-sugar food. We use bioinformatic transcriptional profiling to examine gene co-regulation between peroxisomal genes and other metabolic pathways and we observe that the expression of peroxisomal and carbohydrate pathway genes in flies and mouse are tightly correlated. Indeed key steps in carbohydrate metabolism were found to be strongly co-regulated with peroxisomal genes in flies and mice. Moreover mice lacking peroxisomes exhibit defective carbohydrate metabolism at the same key steps in carbohydrate breakdown. Our data indicate an unexpected link between these two metabolic processes and suggest metabolism of carbohydrates could be a new therapeutic target for patients with PBD.en_US
dc.identifier.citationWangler, Michael F., Chao, Yu-Hsin, Bayat, Vafa, et al.. "Peroxisomal biogenesis is genetically and biochemically linked to carbohydrate metabolism in Drosophila and mouse." <i>PLoS Genetics,</i> 13, no. 6 (2017) Public Library of Science: https://doi.org/10.1371/journal.pgen.1006825.en_US
dc.identifier.digitalPeroxisomal_biogenesisen_US
dc.identifier.doihttps://doi.org/10.1371/journal.pgen.1006825en_US
dc.identifier.urihttps://hdl.handle.net/1911/95629en_US
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.rightsThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titlePeroxisomal biogenesis is genetically and biochemically linked to carbohydrate metabolism in Drosophila and mouseen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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