Regulation of peroxisomal matrix protein import by ubiquitination

Biochim Biophys Acta. 2016 May;1863(5):838-49. doi: 10.1016/j.bbamcr.2015.09.010. Epub 2015 Sep 12.


Peroxisomes are organelles that play an important role in many cellular tasks. The functionality of peroxisomes depends on the proper import of their matrix proteins. Peroxisomal matrix proteins are imported posttranslationally in a folded, sometimes even oligomeric state. They harbor a peroxisomal targeting sequence (PTS), which is recognized by dynamic PTS-receptors in the cytosol. The PTS-receptors ferry the cargo to the peroxisomal membrane, where they become part of a transient import pore and then release the cargo into the peroxisomal lumen. Subsequentially, the PTS-receptors are ubiquitinated in order to mark them for the export-machinery, which releases them back to the cytosol. Upon deubiquitination, the PTS-receptors can facilitate further rounds of cargo import. Because the ubiquitination of the receptors is an essential step in the import cycle, it also represents a central regulatory element that governs peroxisomal dynamics. In this review we want to give an introduction to the functional role played by ubiquitination during peroxisomal protein import and highlight the mechanistic concepts that have emerged based on data derived from different species since the discovery of the first ubiquitinated peroxin 15years ago. Moreover, we discuss future tasks and the potential of using advanced technologies for investigating further details of peroxisomal protein transport.

Keywords: Deubiquitination; Peroxisome; Pex4p; Pex5p; Protein transport; Ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Animals
  • Eukaryotic Cells / chemistry
  • Eukaryotic Cells / metabolism
  • Gene Expression Regulation
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Peroxisomes / chemistry
  • Peroxisomes / metabolism*
  • Plants / chemistry
  • Plants / metabolism
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary
  • Protein Transport
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction
  • Ubiquitin / chemistry
  • Ubiquitin / genetics
  • Ubiquitin / metabolism*
  • Ubiquitination


  • Membrane Proteins
  • Protein Isoforms
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin
  • Adenosine Triphosphatases
  • MSP1 protein, S cerevisiae
  • ATPases Associated with Diverse Cellular Activities
  • PEX1 protein, S cerevisiae
  • PEX6 protein, S cerevisiae