Export-deficient monoubiquitinated PEX5 triggers peroxisome removal in SV40 large T antigen-transformed mouse embryonic fibroblasts

@article{Nordgren2015ExportdeficientMP,
  title={Export-deficient monoubiquitinated PEX5 triggers peroxisome removal in SV40 large T antigen-transformed mouse embryonic fibroblasts},
  author={Marcus Nordgren and T{\^a}nia Francisco and Celien Lismont and Lore Hennebel and Chantal Brees and Bo Wang and Paul P. Van Veldhoven and Jorge E Azevedo and Marc Fransen},
  journal={Autophagy},
  year={2015},
  volume={11},
  pages={1326 - 1340}
}
Peroxisomes are ubiquitous cell organelles essential for human health. To maintain a healthy cellular environment, dysfunctional and superfluous peroxisomes need to be selectively removed. Although emerging evidence suggests that peroxisomes are mainly degraded by pexophagy, little is known about the triggers and molecular mechanisms underlying this process in mammalian cells. In this study, we show that PEX5 proteins fused to a bulky C-terminal tag trigger peroxisome degradation in SV40 large… 

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Peroxisomal monoubiquitinated PEX5 interacts with the AAA ATPases PEX1 and PEX6 and is unfolded during its dislocation into the cytosol

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The peroxisomal exportomer directly inhibits phosphoactivation of the pexophagy receptor Atg36 to suppress pexophagy in yeast

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Peroxisomal ATPase ATAD1 acts in quality control of the protein import machinery

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The peroxisomal AAA ATPase complex prevents pexophagy and development of peroxisome biogenesis disorders

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Peroxisomes as Modulators of Cellular Protein Thiol Oxidation: A New Model System.

The development of a human cell line that can be used to selectively generate H2O2 inside peroxisomes in a time- and dose-controlled manner and the extent of protein oxidation depends on the subcellular location of the target protein and is inversely correlated to catalase activity and cellular glutathione content are reported.

Peroxisome biogenesis and human peroxisome-deficiency disorders

  • Y. Fujiki
  • Biology
    Proceedings of the Japan Academy. Series B, Physical and biological sciences
  • 2016
Successful cloning of PEX genes encoding peroxins required for peroxisome assembly invaluably contributed to the accomplishment of cloning of pathogenic genes responsible for PBDs.

Pexophagy is responsible for 65% of cases of peroxisome biogenesis disorders

Recognizing PEX1, PEX6 and PEX26 as pexophagy suppressors will allow treating patients with a new range of tools designed to target mammalian pexphagy, and raised hope for up to 65% of all PBD patients with various deficiencies in the AAA-complex.
...

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