The peroxisomal protein import machinery displays a preference for monomeric substrates
Author(s)
Type
Journal Article
Abstract
Peroxisomal matrix proteins are synthesized on cytosolic ribosomes and transported by the shuttling receptor PEX5 to the peroxisomal membrane docking/translocation machinery, where they are translocated into the organelle matrix. Under certain experimental conditions this protein import machinery has the remarkable capacity to accept already oligomerized proteins, a property that has heavily influenced current models on the mechanism of peroxisomal protein import. However, whether or not oligomeric proteins are really the best and most frequent clients of this machinery remain unclear. In this work, we present three lines of evidence suggesting that the peroxisomal import machinery displays a preference for monomeric proteins. First, in agreement with previous findings on catalase, we show that PEX5 binds newly synthesized (monomeric) acyl-CoA oxidase 1 (ACOX1) and urate oxidase (UOX), potently inhibiting their oligomerization. Second, in vitro import experiments suggest that monomeric ACOX1 and UOX are better peroxisomal import substrates than the corresponding oligomeric forms. Finally, we provide data strongly suggesting that although ACOX1 lacking a peroxisomal targeting signal can be imported into peroxisomes when co-expressed with ACOX1 containing its targeting signal, this import pathway is inefficient.
Date Issued
2015-04-08
Online Publication Date
2015-04-08
Date Acceptance
2015-03-16
ISSN
2046-2441
Publisher
The Royal Society
Journal / Book Title
Open Biology
Volume
5
Issue
4
Source Database
pubmed
Subjects
PEX5
acyl-CoA oxidase
docking/translocation machinery
peroxisomes
protein import
urate oxidase
Acyl-CoA Oxidase
Animals
Blotting, Western
COS Cells
Cercopithecus aethiops
Cytosol
Humans
Mice
Microscopy, Fluorescence
Models, Biological
Mutation
Peroxisomes
Protein Binding
Protein Multimerization
Protein Transport
Rats
Receptors, Cytoplasmic and Nuclear
Signal Transduction
Urate Oxidase
Publication Status
Published
Article Number
140236