Newly identified Chinese hamster ovary cell mutants are defective in biogenesis of peroxisomal membrane vesicles (peroxisomal ghosts), representing a novel complementation group in mammals

被引:53
作者
Kinoshita, N
Ghaedi, K
Shimozawa, N
Wanders, RJA
Matsuzono, Y
Imanaka, T
Okumoto, K
Suzuki, Y
Kondo, N
Fujiki, Y
机构
[1] Kyushu Univ, Fac Sci, Dept Biol, Higashi Ku, Fukuoka 8128581, Japan
[2] Gifu Univ, Fac Med, Dept Pediat, Gifu 5008076, Japan
[3] Univ Amsterdam, Acad Med Ctr, Dept Pediat, NL-1100 DE Amsterdam, Netherlands
[4] Teikyo Univ, Fac Pharmaceut Sci, Dept Microbiol & Mol Pathol, Sagamiko, Kanagawa 1990211, Japan
[5] Japan Sci & Technol Corp, CREST, Tokyo 1700013, Japan
关键词
D O I
10.1074/jbc.273.37.24122
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We isolated peroxisome biogenesis-defective mutants from Chinese hamster ovary cells by the 9-(1'-pyrene)nonanol/ultraviolet (P90H/UV) method. Seven cell mutants, ZP116, ZP119, ZP160, ZP161, ZP162, ZP164, and ZP165, of 11 P90H/UV-resistant cell clones showed cytosolic localization of catalase, a peroxisomal matrix enzyme, apparently indicating a defect of peroxisome biogenesis. By transfection of PEX cDNAs and cell fusion analysis, mutants ZP119 and ZP165 were found to belong to a novel complementation group (CG), distinct from earlier mutants. CG analysis by cell fusion with fibroblasts from patients with peroxisome biogenesis disorders such as Zellweger syndrome indicated that ZP119 and ZP165 were in the same CG as the most recently identified human CG-J. The peroxisomal matrix proteins examined, including PTS1 proteins as well as a PTS2 protein, 3-ketoacyl-CoA thiolase, were also found in the cytosol its ZP119 and ZP165. Furthermore, these mutants showed typical percdxisorne assembly-defective phenotype such as severe loss of resistance to 12-(1'-pyrene)dodecanoic acid/UV treatment. Most strikingly, peroxisomal reminiscent vesicular structures, so-called peroxisomal ghosts noted in all CGs of earlier Chinese hamster ovary cell mutants as well as in eight CGs of patients' fibroblasts, were not discernible ire ZP119 and ZP165, despite normal synthesis of peroxisomal membrane proteins. Accordingly, ZP119 and ZP165 are the first cell mutants defective in import of both soluble and membrane proteins, representing the 14th peroxisome-deficient CG in mammals, including humans.
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页码:24122 / 24130
页数:9
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