Functional analysis of PEX13 mutation in a Zellweger syndrome spectrum patient reveals novel homooligomerization of PEX13 and its role in human peroxisome biogenesis.

@article{Krause2013FunctionalAO,
  title={Functional analysis of PEX13 mutation in a Zellweger syndrome spectrum patient reveals novel homooligomerization of PEX13 and its role in human peroxisome biogenesis.},
  author={Cindy Krause and Hendrik Rosewich and Andrew Woehler and Jutta G{\"a}rtner},
  journal={Human molecular genetics},
  year={2013},
  volume={22 19},
  pages={
          3844-57
        }
}
In humans, the concerted action of at least 13 different peroxisomal PEX proteins is needed for proper peroxisome biogenesis. Mutations in any of these PEX genes can lead to lethal neurometabolic disorders of the Zellweger syndrome spectrum (ZSS). Previously, we identified the W313G mutation located within the SH3 domain of the peroxisomal protein, PEX13. As this tryptophan residue is highly conserved in almost all known SH3 proteins, we investigated the pathogenic mechanism of the W313G… 
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TLDR
It is demonstrated that PEX13 is required for selective autophagy of Sindbis virus and of damaged mitochondria (mitophagy) and that disease‐associated Pex13 mutants I326T and W313G are defective in mitophagy, and it is suggested that dysregulation of P EX13‐mediatedMitophagy may contribute to ZSS pathogenesis.
A viable Arabidopsis pex13 missense allele confers severe peroxisomal defects and decreases PEX5 association with peroxisomes
TLDR
The pex13-4 mutant provides valuable insight into plant peroxisome receptor docking and matrix protein import and can be improved by increasing PEX5 levels.
Membrane topologies of PEX13 and PEX14 provide new insights on the mechanism of protein import into peroxisomes
TLDR
PEX14 is a bona fide intrinsic membrane protein with a Nin‐Cout topology, and that PEX13 adopts a Nout‐CinTopology, thus exposing its carboxy‐terminal Src homology 3 [SH3] domain into the organelle matrix.
Super-resolution imaging reveals the sub-diffraction phenotype of Zellweger Syndrome ghosts and wild-type peroxisomes
TLDR
The peroxisome morphology in healthy skin fibroblasts and the sub-diffraction phenotype of residualPeroxisomal structures (‘ghosts’) in ZSS patients that revealed a relation between mutation severity and clinical phenotype are defined.
Mild Zellweger syndrome due to a novel PEX6 mutation: correlation between clinical phenotype and in silico prediction of variant pathogenicity
TLDR
In the milder phenotypes, adrenal insufficiency, hypoacusis, and leukodystrophy together seem to be pathognomonic for ZS, and in silico prediction of variant severity suggested its possible benign effect.
Human Disorders of Peroxisome Biogenesis: Zellweger Spectrum and Rhizomelic Chondrodysplasia Punctata
The human peroxisome biogenesis disorders (PBD) are caused by autosomal recessive mutations in any of the 14 PEX genes, which encode peroxins, or PEX proteins, that act cooperatively to assemble…
Characterization of peroxisomes and peroxisome deficient cell lines by super-resolution microscopy and biochemical methods
TLDR
The membrane ghost phenotype associated with Zellweger Syndrome Spectrum disorder could be shown to correlate with the clinical severity and import deficiency in patients’ fibroblasts, and supports the hypothesis that PEX35 regulates peroxisome abundance by an Arf1 dependent vesiculation mechanism.
and Rhizomelic Chondrodysplasia Punctata 4
TLDR
This chapter will review clinical phenotypes, diagnoses, supportive management, and research approaches to developing targeted therapies for human peroxisome biogenesis disorders.
The Matrix Protein Import Complex in Yeast
TLDR
Most recent advances in understanding the formation and function of receptor complexes in the cytosol and at the peroxisomal membrane are reported.
Diagnostic challenges and disease management in patients with a mild Zellweger spectrum disorder phenotype.
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