title: Hepatic dysfunction in peroxisomal disorders.
abstract: The peroxisomal compartment in hepatocytes hosts several essential metabolic conversions. These are defective in peroxisomal disorders that are either caused by failure to import the enzymes in the organelle or by mutations in the enzymes or in transporters needed to transfer the substrates across the peroxisomal membrane. Hepatic pathology is one of the cardinal features in disorders of peroxisome biogenesis and peroxisomal β-oxidation although it only rarely determines the clinical fate. In mouse models of these diseases liver pathologies also occur, although these are not always concordant with the human phenotype which might be due to differences in diet, expression of enzymes and backup mechanisms. Besides the morphological changes, we overview the impact of peroxisome malfunction on other cellular compartments including mitochondria and the ER. We further focus on the metabolic pathways that are affected such as bile acid formation, and dicarboxylic acid and branched chain fatty acid degradation. It appears that the association between deregulated metabolites and pathological events remains unclear.
authors.affiliation: Laboratory for Cell Metabolism, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, B-3000 Leuven, Belgium. Electronic address: myriam.baes@pharm.kuleuven.be.
authors.forename: Myriam
authors.initials: M
authors.lastname: Baes
authors.affiliation: Laboratory for Lipid Biochemistry and Protein Interactions, Department of Cellular and Molecular Medicine, KU Leuven, B-3000 Leuven, Belgium. Electronic address: paul.vanveldhoven@med.kuleuven.be.
authors.forename: Paul P
authors.initials: PP
authors.lastname: Van Veldhoven
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics; D053858:Metabolic Networks and Pathways / Q000235:genetics; D051379:Mice; D008930:Mitochondria, Liver / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D018901:Peroxisomal Disorders / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020675:Peroxisomes / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D015398:Signal Transduction
chemical_list: D008565:Membrane Proteins; C490455:PEX11A protein, human; D020033:Protein Isoforms