Chapter 18 Lessons for peroxisome biogenesis from fluorescence analyses of Zellweger syndrome fibroblasts

Abstract

Abstract Fibroblasts from seven Zellweger syndrome patients belonging to five complementation groups were examined by immunofluorescence with anti-catalase and an antiserum against peroxisomal membrane proteins. Large peroxisomal membrane ghosts were found in all of the samples. Except for one patient, none of the ghosts contained catalase. Other data indicate that the ghosts must be mostly empty. Thus these mutations interfere with the translocation of proteins through the peroxisome membrane, but not with the assembly of the membrane proteins themselves. These are Peroxisome IMport (PIM) mutations. The results show that peroxisome membrane assembly has fewer requirements, or different requirements, than the translocation of peroxisome matrix proteins into the organelle. These mostly empty peroxisome membranes must be able to grow and divide (as normal peroxisomes do), despite their lack of content. Analysis of the immunofluorescence data revealed three distinct fluorescence patterns; provisionally, these appear to depend on which gene is defective. Fusion of fibroblast samples led to the full recovery of normal peroxisome assembly.