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The pathogenic peroxin Pex26p recruits the Pex1p–Pex6p AAA ATPase complexes to peroxisomes

Nature Cell Biology volume 5, pages 454–460 (2003)Cite this article

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 isolated4,5,6,7. 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. Epitope-tagged 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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Figure 1: Cloning of the CG8 pathogenic gene PEX26.
Figure 2: Intracellular localization and membrane topology of Pex26.
Figure 3: Pex26 recruits Pex6–Pex1 complexes to peroxisomes.

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Acknowledgements

We thank M. Obo and S. Furuki for technical assistance; R. Tanaka for preparing figures; members of the Fujiki laboratory for discussion; N. Thomas and A. Moser for comments; A. Kawai, T. Kumashiro, and K. Ghaedi for participating in the initial stage of this work. This work was supported in part by a SORST grant from the Science and Technology Corporation of Japan; Grants-in-Aid for Scientific Research and Grant of National Project on Protein Structural and Functional Analyses (to Y.F.); and by The 21st Century COE Program from the Ministry of Education, Culture, Sports, Science and Technology of Japan, a grant from the Uehara Memorial Foundation, a grant from the Japan Foundation for Applied Enzymology, and a grant (to S.T.) from the Naito Foundation.

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  1. Naomi Matsumoto and Shigehiko Tamura: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Biology, Faculty of Sciences, Kyushu University Graduate School, Fukuoka, 812-8581, Japan

    Naomi Matsumoto, Shigehiko Tamura & Yukio Fujiki

  2. SORST, Japan Science and Technology Corporation, Kawaguchi, 332-0012, Saitama, Japan

    Yukio Fujiki

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  1. Naomi Matsumoto
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Correspondence to Yukio Fujiki.

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Matsumoto, N., Tamura, S. & Fujiki, Y. The pathogenic peroxin Pex26p recruits the Pex1p–Pex6p AAA ATPase complexes to peroxisomes. Nat Cell Biol 5, 454–460 (2003). https://doi.org/10.1038/ncb982

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