Deciphering the potential involvement of PXMP2 and PEX11B in hydrogen peroxide permeation across the peroxisomal membrane reveals a role for PEX11B in protein sorting

Celien Lismont, Janet Koster, Sarah Provost, Myriam Baes, Paul P. van Veldhoven, Hans R. Waterham, Marc Fransen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Peroxisomes have the intrinsic ability to produce and scavenge hydrogen peroxide (H2O2), a diffusible second messenger that controls diverse cellular processes by modulating protein activity through cysteine oxidation. Current evidence indicates that H2O2, a molecule whose physicochemical properties are similar to those of water, traverses cellular membranes through specific aquaporin channels, called peroxiporins. Until now, no peroxiporin-like proteins have been identified in the peroxisomal membrane, and it is widely assumed that small molecules such as H2O2 can freely permeate this membrane through PXMP2, a non-selective pore-forming protein with an upper molecular size limit of 300–600 Da. By employing the CRISPR-Cas9 technology in combination with a Flp-In T-REx 293 cell line that can be used to selectively generate H2O2 inside peroxisomes in a controlled manner, we provide evidence that PXMP2 is not essential for H2O2 permeation across the peroxisomal membrane, neither in control cells nor in cells lacking PEX11B, a peroxisomal membrane-shaping protein whose yeast homologue facilitates the permeation of molecules up to 400 Da. During the course of this study, we unexpectedly noted that inactivation of PEX11B leads to partial localization of both peroxisomal membrane and matrix proteins to mitochondria and a decrease in peroxisome density. These findings are discussed in terms of the formation of a functional peroxisomal matrix protein import machinery in the outer mitochondrial membrane.
Original languageEnglish
Article number182991
JournalBiochimica et Biophysica Acta. Biomembranes
Volume1861
Issue number10
DOIs
Publication statusPublished - 1 Oct 2019
Externally publishedYes

Cite this

@article{3a8e37417b5d4129ae1e0f4f8195af7d,
title = "Deciphering the potential involvement of PXMP2 and PEX11B in hydrogen peroxide permeation across the peroxisomal membrane reveals a role for PEX11B in protein sorting",
abstract = "Peroxisomes have the intrinsic ability to produce and scavenge hydrogen peroxide (H2O2), a diffusible second messenger that controls diverse cellular processes by modulating protein activity through cysteine oxidation. Current evidence indicates that H2O2, a molecule whose physicochemical properties are similar to those of water, traverses cellular membranes through specific aquaporin channels, called peroxiporins. Until now, no peroxiporin-like proteins have been identified in the peroxisomal membrane, and it is widely assumed that small molecules such as H2O2 can freely permeate this membrane through PXMP2, a non-selective pore-forming protein with an upper molecular size limit of 300–600 Da. By employing the CRISPR-Cas9 technology in combination with a Flp-In T-REx 293 cell line that can be used to selectively generate H2O2 inside peroxisomes in a controlled manner, we provide evidence that PXMP2 is not essential for H2O2 permeation across the peroxisomal membrane, neither in control cells nor in cells lacking PEX11B, a peroxisomal membrane-shaping protein whose yeast homologue facilitates the permeation of molecules up to 400 Da. During the course of this study, we unexpectedly noted that inactivation of PEX11B leads to partial localization of both peroxisomal membrane and matrix proteins to mitochondria and a decrease in peroxisome density. These findings are discussed in terms of the formation of a functional peroxisomal matrix protein import machinery in the outer mitochondrial membrane.",
author = "Celien Lismont and Janet Koster and Sarah Provost and Myriam Baes and {van Veldhoven}, {Paul P.} and Waterham, {Hans R.} and Marc Fransen",
year = "2019",
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language = "English",
volume = "1861",
journal = "Biochimica et Biophysica Acta. Biomembranes",
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Deciphering the potential involvement of PXMP2 and PEX11B in hydrogen peroxide permeation across the peroxisomal membrane reveals a role for PEX11B in protein sorting. / Lismont, Celien; Koster, Janet; Provost, Sarah; Baes, Myriam; van Veldhoven, Paul P.; Waterham, Hans R.; Fransen, Marc.

In: Biochimica et Biophysica Acta. Biomembranes, Vol. 1861, No. 10, 182991, 01.10.2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Deciphering the potential involvement of PXMP2 and PEX11B in hydrogen peroxide permeation across the peroxisomal membrane reveals a role for PEX11B in protein sorting

AU - Lismont, Celien

AU - Koster, Janet

AU - Provost, Sarah

AU - Baes, Myriam

AU - van Veldhoven, Paul P.

AU - Waterham, Hans R.

AU - Fransen, Marc

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Peroxisomes have the intrinsic ability to produce and scavenge hydrogen peroxide (H2O2), a diffusible second messenger that controls diverse cellular processes by modulating protein activity through cysteine oxidation. Current evidence indicates that H2O2, a molecule whose physicochemical properties are similar to those of water, traverses cellular membranes through specific aquaporin channels, called peroxiporins. Until now, no peroxiporin-like proteins have been identified in the peroxisomal membrane, and it is widely assumed that small molecules such as H2O2 can freely permeate this membrane through PXMP2, a non-selective pore-forming protein with an upper molecular size limit of 300–600 Da. By employing the CRISPR-Cas9 technology in combination with a Flp-In T-REx 293 cell line that can be used to selectively generate H2O2 inside peroxisomes in a controlled manner, we provide evidence that PXMP2 is not essential for H2O2 permeation across the peroxisomal membrane, neither in control cells nor in cells lacking PEX11B, a peroxisomal membrane-shaping protein whose yeast homologue facilitates the permeation of molecules up to 400 Da. During the course of this study, we unexpectedly noted that inactivation of PEX11B leads to partial localization of both peroxisomal membrane and matrix proteins to mitochondria and a decrease in peroxisome density. These findings are discussed in terms of the formation of a functional peroxisomal matrix protein import machinery in the outer mitochondrial membrane.

AB - Peroxisomes have the intrinsic ability to produce and scavenge hydrogen peroxide (H2O2), a diffusible second messenger that controls diverse cellular processes by modulating protein activity through cysteine oxidation. Current evidence indicates that H2O2, a molecule whose physicochemical properties are similar to those of water, traverses cellular membranes through specific aquaporin channels, called peroxiporins. Until now, no peroxiporin-like proteins have been identified in the peroxisomal membrane, and it is widely assumed that small molecules such as H2O2 can freely permeate this membrane through PXMP2, a non-selective pore-forming protein with an upper molecular size limit of 300–600 Da. By employing the CRISPR-Cas9 technology in combination with a Flp-In T-REx 293 cell line that can be used to selectively generate H2O2 inside peroxisomes in a controlled manner, we provide evidence that PXMP2 is not essential for H2O2 permeation across the peroxisomal membrane, neither in control cells nor in cells lacking PEX11B, a peroxisomal membrane-shaping protein whose yeast homologue facilitates the permeation of molecules up to 400 Da. During the course of this study, we unexpectedly noted that inactivation of PEX11B leads to partial localization of both peroxisomal membrane and matrix proteins to mitochondria and a decrease in peroxisome density. These findings are discussed in terms of the formation of a functional peroxisomal matrix protein import machinery in the outer mitochondrial membrane.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/31129117

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DO - 10.1016/j.bbamem.2019.05.013

M3 - Article

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JO - Biochimica et Biophysica Acta. Biomembranes

JF - Biochimica et Biophysica Acta. Biomembranes

SN - 0005-2736

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