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Peroxisome assembly mutations in humans: Structural heterogeneity in Zellweger syndrome
Author(s) -
Santos Manuel J.,
Hoefler Sigrid,
Moser Ann B.,
Moser Hugo W.,
Lazarow Paul B.
Publication year - 1992
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041510115
Subject(s) - zellweger syndrome , complementation , peroxisome , biology , biogenesis , organelle , peroxisomal disorder , microbiology and biotechnology , mutation , genetics , gene , phenotype
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. © 1992 Wiley‐Liss, Inc.