title: Peroxisome assembly mutations in humans: structural heterogeneity in Zellweger syndrome.
abstract: Empty membrane ghosts of peroxisomes were found in fibroblasts from a patient with Zellweger's syndrome, a genetic disease of humans (Santos et al: Science 239:1536-1538, 1988). Import of soluble matrix proteins into the organelle was defective. We have now studied fibroblasts from seven patients representing five complementation groups of the syndrome (defined by complementation for peroxisome enzyme function). We find that empty peroxisome ghosts are present in all seven cell samples. Three patients, representing three complementation groups, give the same membrane pattern by immunofluorescence: few large ghosts. Three other patients, representing two complementation groups, give a second pattern: many large ghosts. The seventh patient's pattern is distinct. Thus, all seven of these patients exhibit Peroxisome IMport (PIM) mutations. Since membrane assembly occurs in these cells, the results indicate that biogenesis of organelle content and membrane proteins proceed by different mechanisms. Growth and division of the empty peroxisomal membrane must occur, but are modified by the mutations (ghost size and abundance vary). Cell fusion and immunofluorescence analyses of peroxisome size and catalase packaging formally demonstrate genetic complementation groups for peroxisome assembly in Zellweger syndrome.
authors.affiliation: Department of Cell Biology and Anatomy, Mount Sinai School of Medicine, New York, New York 10029.
authors.forename: M J
authors.initials: MJ
authors.lastname: Santos
authors.forename: S
authors.initials: S
authors.lastname: Hoefler
authors.forename: A B
authors.initials: AB
authors.lastname: Moser
authors.forename: H W
authors.initials: HW
authors.lastname: Moser
authors.forename: P B
authors.initials: PB
authors.lastname: Lazarow
mesh_terms: D002374:Catalase / Q000032:analysis; D002462:Cell Membrane / Q000737:chemistry / Q000648:ultrastructure; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D006801:Humans; D008830:Microbodies / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics*; D015388:Organelles / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D015211:Zellweger Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D002374:Catalase