title: Metabolic control of peroxisome abundance.
abstract: Zellweger syndrome and related disorders represent a group of lethal, genetically heterogeneous diseases. These peroxisome biogenesis disorders (PBDs) are characterized by defective peroxisomal matrix protein import and comprise at least 10 complementation groups. The genes defective in seven of these groups and more than 90% of PBD patients are now known. Here we examine the distribution of peroxisomal membrane proteins in fibroblasts from PBD patients representing the seven complementation groups for which the mutant gene is known. Peroxisomes were detected in all PBD cells, indicating that the ability to form a minimal peroxisomal structure is not blocked in these mutants. We also observed that peroxisome abundance was reduced fivefold in PBD cells that are defective in the PEX1, PEX5, PEX12, PEX6, PEX10, and PEX2 genes. These cell lines all display a defect in the import of proteins with the type-1 peroxisomal targeting signal (PTS1). In contrast, peroxisome abundance was unaffected in cells that are mutated in PEX7 and are defective only in the import of proteins with the type-2 peroxisomal targeting signal. Interestingly, a fivefold reduction in peroxisome abundance was also observed for cells lacking either of two PTS1-targeted peroxisomal beta-oxidation enzymes, acyl-CoA oxidase and 2-enoyl-CoA hydratase/D-3-hydroxyacyl-CoA dehydrogenase. These results indicate that reduced peroxisome abundance in PBD cells may be caused by their inability to import these PTS1-containing enzymes. Furthermore, the fact that peroxisome abundance is influenced by peroxisomal 105-oxidation activities suggests that there may be metabolic control of peroxisome abundance.
authors.affiliation: The Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Chang
authors.forename: S
authors.initials: S
authors.lastname: South
authors.forename: D
authors.initials: D
authors.lastname: Warren
authors.forename: J
authors.initials: J
authors.lastname: Jones
authors.forename: A B
authors.initials: AB
authors.lastname: Moser
authors.forename: H W
authors.initials: HW
authors.lastname: Moser
authors.forename: S J
authors.initials: SJ
authors.lastname: Gould
mesh_terms: D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology; D008830:Microbodies / Q000502:physiology*; D018901:Peroxisomal Disorders / Q000209:etiology / Q000378:metabolism*; D000074437:Peroxisomal Targeting Signal 2 Receptor; D000074435:Peroxisome-Targeting Signal 1 Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D015211:Zellweger Syndrome / Q000209:etiology
chemical_list: D008565:Membrane Proteins; C490455:PEX11A protein, human; C490453:PEX11B protein, human; C000614264:PEX5 protein, human; C000614269:PEX7 protein, human; D000074437:Peroxisomal Targeting Signal 2 Receptor; D000074435:Peroxisome-Targeting Signal 1 Receptor; D018160:Receptors, Cytoplasmic and Nuclear