+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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



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



Autophagy 13(5): 991-994



Peroxisome biogenesis disorders (PBDs) is a group of diseases caused by mutations in one of the peroxins, proteins responsible for biogenesis of the peroxisomes. In recent years, it became clear that many peroxins (e.g., PEX3 and PEX14) play additional roles in peroxisome homeostasis (such as promoting autophagic degradation of peroxisomes or pexophagy), which are often opposite to their originally established functions in peroxisome formation and maintenance. Even more interesting, the peroxins that make up the peroxisomal AAA ATPase complex (AAA-complex) in yeast (Pex1, Pex6 and Pex15) or mammals (PEX1, PEX6, PEX26) are responsible for the downregulation of pexophagy. Moreover, this might be even their primary role in human: to prevent pexophagy by removing from the peroxisomal membrane the ubiquitinated peroxisomal matrix protein import receptor, Ub-PEX5, which is also a signal for the Ub-binding pexophagy receptor, NBR1. Remarkably, the peroxisomes rescued from pexophagy by autophagic inhibitors in PEX1G843D (the most common PBD mutation) cells are able to import matrix proteins and improve their biochemical function suggesting that the AAA-complex per se is not essential for the protein import function in human. This paradigm-shifting discovery published in the current issue of Autophagy has raised hope for up to 65% of all PBD patients with various deficiencies in the AAA-complex. Recognizing PEX1, PEX6 and PEX26 as pexophagy suppressors will allow treating these patients with a new range of tools designed to target mammalian pexophagy.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 060085570

Download citation: RISBibTeXText

PMID: 28318378

DOI: 10.1080/15548627.2017.1291480


Related references

The peroxisomal AAA ATPase complex prevents pexophagy and development of peroxisome biogenesis disorders. Autophagy 13(5): 868-884, 2017

Peroxisome assembly factor-2 A novel human responsible gene for group C peroxisome biogenesis disorders. American Journal of Human Genetics 59(4 Suppl. ): A207, 1996

Mutation analysis of PXAAA1, a new peroxisome assembly gene responsible for a subgroup of the peroxisome biogenesis disorders. American Journal of Human Genetics 59(4 Suppl. ): A4, 1996

Human peroxisome assembly factor-2 (PAF-2): a gene responsible for group C peroxisome biogenesis disorder in humans. American Journal of Human Genetics 59(6): 1210-1220, 1996

Mutations in the peroxin Pex26p responsible for peroxisome biogenesis disorders of complementation group 8 impair its stability, peroxisomal localization, and interaction with the Pex1p x Pex6p complex. Journal of Biological Chemistry 281(3): 1317-1323, 2006

Mutations in the Peroxin Pex26p Responsible for Peroxisome Biogenesis Disorders of Complementation Group 8 Impair Its Stability, Peroxisomal Localization, and Interaction with the Pex1p.Pex6p Complex. Journal of biological chemistry20 281(3): 1317-1323, 2006

Approaches to studies on peroxisome biogenesis and human peroxisome-deficient disorders. Annals of the new York Academy of Sciences 804: 491-501, 1996

Temperature sensitivity in peroxisome assembly processes characterizes milder forms of peroxisome biogenesis disorders. Cell Biochemistry & Biophysics 32: 165-170, Spring, 2000

Temperature sensitivity in peroxisome assembly processes characterizes milder forms of peroxisome biogenesis disorders. Cell Biochemistry and Biophysics 32 Spring: 165-170, 2000

Peroxisome biogenesis and molecular defects in peroxisome assembly disorders. Cell Biochemistry and Biophysics 32 Spring: 155-164, 2000

Peroxisome biogenesis and molecular defects in peroxisome assembly disorders. Cell Biochemistry & Biophysics 32: 155-164, Spring, 2000

Peroxisome biogenesis disorders: identification of a new complementation group distinct from peroxisome-deficient CHO mutants and not complemented by human PEX 13. Biochemical and Biophysical Research Communications 243(2): 368-371, 1998

Temperature-sensitive phenotypes of peroxisome-assembly processes represent the milder forms of human peroxisome-biogenesis disorders. American Journal of Human Genetics 62(6): 1539-1543, 1998

Genomic structure and identification of 11 novel mutations of the PEX6 (peroxisome assembly factor-2) gene in patients with peroxisome biogenesis disorders. Human Mutation 13(6): 487-496, 1999

Peroxisome biogenesis and human peroxisome-deficiency disorders. Proceedings of the Japan Academy. Series B Physical and Biological Sciences 92(10): 463-477, 2016