Abstract
ABSTRACT: 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 punc-tata (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 β-oxidation, 3-ketoacyl-CoA thiolase (β-keto-thiolase), was present in precursor rather than mature form in both of these diseases. Immunofluorescent staining for peroxisomal β-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).
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Balfe, A., Hoefler, G., Chen, W. et al. Aberrant Subcellular Localization of Peroxisomal 3-Ketoacyl-CoA Thiolase in the Zellweger Syndrome and Rhizomelic Chondrodysplasia Punctata. Pediatr Res 27, 304–310 (1990). https://doi.org/10.1203/00006450-199003000-00023
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1203/00006450-199003000-00023
This article is cited by
-
Rhizomelic chondrodysplasia punctata is caused by deficiency of human PEX7, a homologue of the yeast PTS2 receptor
Nature Genetics (1997)
-
Isolated dihydroxyacetonephosphate-acyl-transferase deficiency in rhizomelic chondrodysplasia punctata: clinical presentation, metabolic and histological findings
European Journal of Pediatrics (1996)
-
In situ heterogeneity of peroxisomal oxidase activities: An update
The Histochemical Journal (1996)
-
Resistance to erucic acid as a selectable marker for peroxisomal activity: Isolation of revertants of an infantile Refsum disease cell line
Journal of Inherited Metabolic Disease (1994)
-
Signals on proteins, intracellular targeting and inborn errors of organellar metabolism
Journal of Inherited Metabolic Disease (1994)