Fibroblasts from patients with the inherited disorder
Zellweger syndrome have few or no peroxisomes; multiple biochemical processes that normally occur in this organelle are defective.
Rhizomelic chondrodysplasia punctata (RCDP) is another inherited disorder in which two unrelated peroxisomal metabolic processes,
plasmalogen synthesis and
phytanic acid oxidation, are impaired despite the normal appearance of peroxisomal structure. It was previously reported that one of the
enzymes of peroxisomal
fatty acid beta-oxidation, 3-ketoacyl-CoA thiolase (beta-keto-thiolase), was present in precursor rather than mature form in both of these diseases. Immunofluorescent staining for peroxisomal
beta-ketothiolase showed the immunoreactivity to be localized in subcellular particles in fibroblasts from both
Zellweger syndrome and RCDP patients, even though the former lack normal peroxisomes. Immunoblot studies were performed to determine the subcellular location of the thiolase precursor in fractionated fibroblasts from Zellweger and RCDP patients. In both disorders, thiolase immunoreactivity was detected in subcellular fractions having a lower density than normal peroxisomes and mitochondria, and was resistant to digestion by
proteinase K. The density of the thiolase precursor-containing fractions was similar to that of peroxisomal membrane "ghost" fractions recently described by Santos et al. (J Biol Chem 263:10502-10509, 1988). Our results suggest that these are not empty membrane vesicles but contain at least one peroxisomal matrix
protein. Furthermore, they exist not only in cells in which normal peroxisomes fail to form (
Zellweger syndrome), but also in some cells which have
catalase-containing peroxisomes (RCDP).