Peroxisomal core structures segregate diverse metabolic pathways

Abstract Peroxisomes are single membrane-bounded oxidative organelles with various metabolic functions including β-oxidation of fatty acids. Peroxisomes of many species confine certain metabolic enzymes into sub-compartments sometimes visible as electron dense cores. Why these structures form is lar...

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Main Authors: Nils Bäcker, Julia Ast, Domenica Martorana, Christian Renicke, Jil Berger, Cristopher-Nils Mais, Marvin Christ, Thorsten Stehlik, Thomas Heimerl, Valentin Wernet, Christof Taxis, Jan Pané-Farré, Michael Bölker, Judith M. Klatt, Björn Sandrock, Kay Oliver Schink, Gert Bange, Johannes Freitag
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-57053-9
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author Nils Bäcker
Julia Ast
Domenica Martorana
Christian Renicke
Jil Berger
Cristopher-Nils Mais
Marvin Christ
Thorsten Stehlik
Thomas Heimerl
Valentin Wernet
Christof Taxis
Jan Pané-Farré
Michael Bölker
Judith M. Klatt
Björn Sandrock
Kay Oliver Schink
Gert Bange
Johannes Freitag
author_facet Nils Bäcker
Julia Ast
Domenica Martorana
Christian Renicke
Jil Berger
Cristopher-Nils Mais
Marvin Christ
Thorsten Stehlik
Thomas Heimerl
Valentin Wernet
Christof Taxis
Jan Pané-Farré
Michael Bölker
Judith M. Klatt
Björn Sandrock
Kay Oliver Schink
Gert Bange
Johannes Freitag
author_sort Nils Bäcker
collection DOAJ
description Abstract Peroxisomes are single membrane-bounded oxidative organelles with various metabolic functions including β-oxidation of fatty acids. Peroxisomes of many species confine certain metabolic enzymes into sub-compartments sometimes visible as electron dense cores. Why these structures form is largely unknown. Here, we report that in the smut fungus Ustilago maydis detergent resistant core structures are enriched for different enzymes excluding several key enzymes of the β-oxidation pathway. This confinement contributes to generation of peroxisome subpopulations that differ in their enzyme content. We identify short amino acid motifs necessary and sufficient for protein self-assembly into aggregates in vitro. The motifs trigger enrichment in cores in vivo and are active in mammalian cells. Perturbation of core assembly via variation of such motifs affects peroxisome function in U. maydis strains challenged with fatty acids. Thus, protein core structures serve to compartmentalize the lumen of peroxisomes thereby preventing interference of biochemical reactions. Metabolic compartmentalization of peroxisomes via assembly of specific proteins may occur in other organisms as well.
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spelling doaj-art-277df0c4a8d04c409a070aa8bb8fb9fb2025-08-20T02:15:00ZengNature PortfolioNature Communications2041-17232025-02-0116111610.1038/s41467-025-57053-9Peroxisomal core structures segregate diverse metabolic pathwaysNils Bäcker0Julia Ast1Domenica Martorana2Christian Renicke3Jil Berger4Cristopher-Nils Mais5Marvin Christ6Thorsten Stehlik7Thomas Heimerl8Valentin Wernet9Christof Taxis10Jan Pané-Farré11Michael Bölker12Judith M. Klatt13Björn Sandrock14Kay Oliver Schink15Gert Bange16Johannes Freitag17Center for Synthetic Microbiology (SYNMIKRO), Philipps-University MarburgDepartment of Biology, Philipps-University MarburgDepartment of Biology, Philipps-University MarburgDepartment of Biology, Philipps-University MarburgCenter for Synthetic Microbiology (SYNMIKRO), Philipps-University MarburgCenter for Synthetic Microbiology (SYNMIKRO), Philipps-University MarburgCenter for Synthetic Microbiology (SYNMIKRO), Philipps-University MarburgDepartment of Biology, Philipps-University MarburgCenter for Synthetic Microbiology (SYNMIKRO), Philipps-University MarburgDepartment of Microbiology, Institute for Applied Biosciences, KITCenter for Synthetic Microbiology (SYNMIKRO), Philipps-University MarburgCenter for Synthetic Microbiology (SYNMIKRO), Philipps-University MarburgCenter for Synthetic Microbiology (SYNMIKRO), Philipps-University MarburgCenter for Synthetic Microbiology (SYNMIKRO), Philipps-University MarburgDepartment of Biology, Philipps-University MarburgCentre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, MontebelloCenter for Synthetic Microbiology (SYNMIKRO), Philipps-University MarburgCenter for Synthetic Microbiology (SYNMIKRO), Philipps-University MarburgAbstract Peroxisomes are single membrane-bounded oxidative organelles with various metabolic functions including β-oxidation of fatty acids. Peroxisomes of many species confine certain metabolic enzymes into sub-compartments sometimes visible as electron dense cores. Why these structures form is largely unknown. Here, we report that in the smut fungus Ustilago maydis detergent resistant core structures are enriched for different enzymes excluding several key enzymes of the β-oxidation pathway. This confinement contributes to generation of peroxisome subpopulations that differ in their enzyme content. We identify short amino acid motifs necessary and sufficient for protein self-assembly into aggregates in vitro. The motifs trigger enrichment in cores in vivo and are active in mammalian cells. Perturbation of core assembly via variation of such motifs affects peroxisome function in U. maydis strains challenged with fatty acids. Thus, protein core structures serve to compartmentalize the lumen of peroxisomes thereby preventing interference of biochemical reactions. Metabolic compartmentalization of peroxisomes via assembly of specific proteins may occur in other organisms as well.https://doi.org/10.1038/s41467-025-57053-9
spellingShingle Nils Bäcker
Julia Ast
Domenica Martorana
Christian Renicke
Jil Berger
Cristopher-Nils Mais
Marvin Christ
Thorsten Stehlik
Thomas Heimerl
Valentin Wernet
Christof Taxis
Jan Pané-Farré
Michael Bölker
Judith M. Klatt
Björn Sandrock
Kay Oliver Schink
Gert Bange
Johannes Freitag
Peroxisomal core structures segregate diverse metabolic pathways
Nature Communications
title Peroxisomal core structures segregate diverse metabolic pathways
title_full Peroxisomal core structures segregate diverse metabolic pathways
title_fullStr Peroxisomal core structures segregate diverse metabolic pathways
title_full_unstemmed Peroxisomal core structures segregate diverse metabolic pathways
title_short Peroxisomal core structures segregate diverse metabolic pathways
title_sort peroxisomal core structures segregate diverse metabolic pathways
url https://doi.org/10.1038/s41467-025-57053-9
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