Abstract
Peroxisomes are ubiquitous organelles with a single membrane that contain over 50 different enzymes that catalyse various metabolic pathways, including β-oxidation and lipid synthesis1. Peroxisome biogenesis disorders (PBDs), such as Zellweger syndrome and neonatal adrenoleukodystrophy, are fatal genetic diseases that are autosomal recessive2,3 . Among the PBDs of the 12 complementation groups (CGs)4, 11 associated PEX genes have been isolated4-7 . Accordingly, only the PBD pathogenic gene for CG8 (also called CG-A) remains unidentified. Here we have isolated human PEX26 encoding a type II peroxisomal membrane protein of relative molecular mass 34,000 (Mr 34K) by using ZP167 cells, a Chinese hamster ovary (CHO) mutant cell line5,8. Expression of PEX26 restores peroxisomal protein import in the fibroblasts of an individual with PBD of CG8. This individual possesses a homozygous, inactivating pathogenic point mutation, Arg98Trp, in Pex26. Pex6 and Pex1 of the AAA ATPase family co-immunoprecipitate with Pex26. Epitopetagged Pex6 and Pex1 are discernible as puncta in normal CHO-K1 cells, but not in PEX26-defective cells. PEX26 expression in ZP167 cells re-establishes colocalization of Pex6 and Pex1 with Pex26, in a Pex6-dependent manner. Thus, Pex26 recruits Pex6-Pex1 complexes to peroxisomes.
| Original language | English |
|---|---|
| Pages (from-to) | 454-460 |
| Number of pages | 7 |
| Journal | Nature Cell Biology |
| Volume | 5 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 1 2003 |
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All Science Journal Classification (ASJC) codes
- Cell Biology
Cite this
The pathogenic peroxin Pex26p recruits the Pex1p-Pex6p AAA ATPase complexes to peroxisomes. / Matsumoto, Naomi; Tamura, Shigehiko; Fujiki, Yukio.
In: Nature Cell Biology, Vol. 5, No. 5, 01.05.2003, p. 454-460.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The pathogenic peroxin Pex26p recruits the Pex1p-Pex6p AAA ATPase complexes to peroxisomes
AU - Matsumoto, Naomi
AU - Tamura, Shigehiko
AU - Fujiki, Yukio
PY - 2003/5/1
Y1 - 2003/5/1
N2 - Peroxisomes are ubiquitous organelles with a single membrane that contain over 50 different enzymes that catalyse various metabolic pathways, including β-oxidation and lipid synthesis1. Peroxisome biogenesis disorders (PBDs), such as Zellweger syndrome and neonatal adrenoleukodystrophy, are fatal genetic diseases that are autosomal recessive2,3 . Among the PBDs of the 12 complementation groups (CGs)4, 11 associated PEX genes have been isolated4-7 . Accordingly, only the PBD pathogenic gene for CG8 (also called CG-A) remains unidentified. Here we have isolated human PEX26 encoding a type II peroxisomal membrane protein of relative molecular mass 34,000 (Mr 34K) by using ZP167 cells, a Chinese hamster ovary (CHO) mutant cell line5,8. Expression of PEX26 restores peroxisomal protein import in the fibroblasts of an individual with PBD of CG8. This individual possesses a homozygous, inactivating pathogenic point mutation, Arg98Trp, in Pex26. Pex6 and Pex1 of the AAA ATPase family co-immunoprecipitate with Pex26. Epitopetagged Pex6 and Pex1 are discernible as puncta in normal CHO-K1 cells, but not in PEX26-defective cells. PEX26 expression in ZP167 cells re-establishes colocalization of Pex6 and Pex1 with Pex26, in a Pex6-dependent manner. Thus, Pex26 recruits Pex6-Pex1 complexes to peroxisomes.
AB - Peroxisomes are ubiquitous organelles with a single membrane that contain over 50 different enzymes that catalyse various metabolic pathways, including β-oxidation and lipid synthesis1. Peroxisome biogenesis disorders (PBDs), such as Zellweger syndrome and neonatal adrenoleukodystrophy, are fatal genetic diseases that are autosomal recessive2,3 . Among the PBDs of the 12 complementation groups (CGs)4, 11 associated PEX genes have been isolated4-7 . Accordingly, only the PBD pathogenic gene for CG8 (also called CG-A) remains unidentified. Here we have isolated human PEX26 encoding a type II peroxisomal membrane protein of relative molecular mass 34,000 (Mr 34K) by using ZP167 cells, a Chinese hamster ovary (CHO) mutant cell line5,8. Expression of PEX26 restores peroxisomal protein import in the fibroblasts of an individual with PBD of CG8. This individual possesses a homozygous, inactivating pathogenic point mutation, Arg98Trp, in Pex26. Pex6 and Pex1 of the AAA ATPase family co-immunoprecipitate with Pex26. Epitopetagged Pex6 and Pex1 are discernible as puncta in normal CHO-K1 cells, but not in PEX26-defective cells. PEX26 expression in ZP167 cells re-establishes colocalization of Pex6 and Pex1 with Pex26, in a Pex6-dependent manner. Thus, Pex26 recruits Pex6-Pex1 complexes to peroxisomes.
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UR - http://www.scopus.com/inward/citedby.url?scp=0038394714&partnerID=8YFLogxK
U2 - 10.1038/ncb982
DO - 10.1038/ncb982
M3 - Article
C2 - 12717447
AN - SCOPUS:0038394714
VL - 5
SP - 454
EP - 460
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 5
ER -