title: Catalase-less peroxisomes. Implication in the milder forms of peroxisome biogenesis disorder.
abstract: We established a Chinese hamster ovary cell line having a temperature-sensitive phenotype in peroxisome biogenesis. This mutant (65TS) was produced by transforming a PEX2-defective mutant, Z65, with a mutant PEX2 gene, PEX2(E55K), derived from a patient with infantile Refsum disease, a milder form of peroxisome biogenesis disorder. In 65TS, catalase was found in the cytosol at a nonpermissive temperature (39 degrees C), but upon the shift to a permissive temperature (33 degrees C), catalase gradually localized to the structures containing a 70-kDa peroxisomal membrane protein, PMP70. In contrast to catalase, other matrix proteins containing typical peroxisome targeting signals, acyl-CoA oxidase and peroxisomal 3-ketoacyl-CoA thiolase, were co-localized with PMP70 in most cells, even at 39 degrees C. We found that these structures are partially functional peroxisomes and named them "catalase-less peroxisomes." Catalase-less peroxisomes were also observed in human fibroblasts from patients with milder forms of peroxisome biogenesis disorder, including the one from which the mutant PEX2 gene was derived. We suggest that these structures are the causes of the milder phenotypes of the patients. Temperature-dependent restoration of the peroxisomes in 65TS occurred even in the presence of cycloheximide, a protein synthesis inhibitor. Thus, we conclude that in 65TS, catalase-less peroxisomes are the direct precursors of peroxisomes.
authors.affiliation: Department of Life Science, Faculty of Science, Himeji Institute of Technology, 3-2-1 Koto, Kamigori, Hyogo 678-1297, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Fujiwara
authors.forename: A
authors.initials: A
authors.lastname: Imamura
authors.forename: N
authors.initials: N
authors.lastname: Hashiguchi
authors.forename: N
authors.initials: N
authors.lastname: Shimozawa
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: N
authors.initials: N
authors.lastname: Kondo
authors.forename: T
authors.initials: T
authors.lastname: Imanaka
authors.forename: T
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: T
authors.initials: T
authors.lastname: Osumi
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000818:Animals; D016466:CHO Cells; D002374:Catalase / Q000502:physiology*; D006224:Cricetinae; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008830:Microbodies / Q000235:genetics; D000074428:Peroxisomal Biogenesis Factor 2; D020675:Peroxisomes / Q000201:enzymology*; D010641:Phenotype; D013696:Temperature
chemical_list: C063305:ABCD3 protein, human; D018528:ATP-Binding Cassette Transporters; D008565:Membrane Proteins; C000614230:PEX2 protein, human; D000074428:Peroxisomal Biogenesis Factor 2; D002374:Catalase