Failure of microtubule-mediated peroxisome division and trafficking in disorders with reduced peroxisome abundance

Nguyen, Tam, Bjorkman, Jonas, Paton, Barbara C. and Crane, Denis I. (2006) Failure of microtubule-mediated peroxisome division and trafficking in disorders with reduced peroxisome abundance. Journal of Cell Science, 119 4: 636-645. doi:10.1242/jcs.02776

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Author Nguyen, Tam
Bjorkman, Jonas
Paton, Barbara C.
Crane, Denis I.
Title Failure of microtubule-mediated peroxisome division and trafficking in disorders with reduced peroxisome abundance
Journal name Journal of Cell Science   Check publisher's open access policy
ISSN 0021-9533
Publication date 2006-02
Sub-type Article (original research)
DOI 10.1242/jcs.02776
Open Access Status File (Publisher version)
Volume 119
Issue 4
Start page 636
End page 645
Total pages 10
Place of publication Cambridge, U.K.
Publisher Company of Biologists
Language eng
Subject 06 Biological Sciences
0601 Biochemistry and Cell Biology
Formatted abstract
In contrast to peroxisomes in normal cells, remnant peroxisomes in cultured skin fibroblasts from a subset of the clinically severe peroxisomal disorders that includes the biogenesis disorder Zellweger syndrome and the single-enzyme defect D-bifunctional protein (D-BP) deficiency, are enlarged and significantly less abundant. We tested whether these features could be related to the known role of microtubules in peroxisome trafficking in mammalian cells. We found that remnant peroxisomes in fibroblasts from patients with PEX1-null Zellweger syndrome or D-BP deficiency exhibited clustering and loss of alignment along peripheral microtubules. Similar effects were observed for both cultured embryonic fibroblasts and brain neurons from a PEX13-null mouse with a Zellweger-syndrome-like phenotype, and a less-pronounced effect was observed for fibroblasts from an infantile Refsum patient who was homozygous for a milder PEX1 mutation. By contrast, such changes were not seen for patients with peroxisomal disorders characterized by normal peroxisome abundance and size. Stable overexpression of PEX11ß to induce peroxisome proliferation largely re-established the alignment of peroxisomal structures along peripheral microtubules in both PEX1-null and D-BP-deficient cells. In D-BP-deficient cells, peroxisome division was apparently driven to completion, as induced peroxisomal structures were similar to the spherical parental structures. By contrast, in PEX1-null cells the majority of induced peroxisomal structures were elongated and tubular. These structures were apparently blocked at the division step, despite having recruited DLP1, a protein necessary for peroxisome fission. These findings indicate that the increased size, reduced abundance, and disturbed cytoplasmic distribution of peroxisomal structures in PEX1-null and D-BP-deficient cells reflect defects at different stages in peroxisome proliferation and division, processes that require association of these structures with, and dispersal along, microtubules. © The Company of Biologists Ltd 2006.
Keyword Peroxisome biogenesis
Peroxisomal disorders
Organelle division
Microtubule trafficking
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 23 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 29 times in Scopus Article | Citations
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Created: Wed, 06 Jan 2010, 15:58:16 EST by Tara Johnson on behalf of Queensland Brain Institute