Peroxisome lifecycle and matrix protein import module

Peroxisomes are maintained by coordinated membrane-protein delivery, matrix cargo recognition, receptor docking and translocation at the importomer, ubiquitin-dependent receptor recycling, membrane growth and division, and import of resident metabolic enzymes. This module captures the conserved peroxin roles and the major route variants that support peroxisome assembly, inheritance, and function across eukaryotes.

MODULE:peroxisome_lifecycleDRAFTOrganelle Lifecyclemodules/peroxisome-lifecycle.yaml
peroxisome organizationGO:0007031 peroxisomeGO:0005777
file:modules/peroxisome-lifecycle-deep-research-falcon.md
Peroxisome lifecycle and matrix protein import module deep research
Falcon deep research synthesis used to refine the module boundaries, importomer/exportomer distinction, lineage variants, and 2023-2024 mechanistic updates.
DOI:10.1016/j.tcb.2023.08.005
Towards solving the mystery of peroxisomal matrix protein import
Supports the coupled import-receptor recycling cycle and the current PEX13/YG-repeat meshwork model for matrix protein import.
DOI:10.1007/s00418-023-02259-5
The peroxisome: an update on mysteries 3.0
Supports the current conserved peroxin skeleton, lineage-specific peroxin variants, peroxisome proliferation/division machinery, and organelle contact-site context.
PMID:28765278
Supports treating the peroxisomal docking/translocation machinery as an importomer module.
PMID:35768507
Supports a distinct ATP-dependent matrix import receptor recycling/extraction module.

This module treats matrix import as a coupled import-export cycle. The docking/translocation importomer is modeled separately from the receptor ubiquitination and ATP-dependent extraction machinery, even though some literature uses "importomer" more broadly. Pexophagy and organelle contact sites are represented as interfaces to the lifecycle, not as part of the core matrix import mechanism.

20Nodes
9Parts
5Variant Sets
10Variants
14Annotons
8Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • peroxisome-lifecycle-deep-research-falcon.md (falcon)

Leaf nodes lacking representative members

5 leaf node(s) with no concrete protein grounding:

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (16/18 grounded genes reviewed)

13 complete review(s) · 16 with deep research · 2 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
human DNM1L (DRP1) O00429 ✗ — —
PEX1 O43933 ✓ ✓ ✓
PEX10 O60683 ✓ ✓ ✓
PEX11A O75192 ✓ ✓ ✓
PEX11B O96011 ✓ ✓ ✓
PEX11G Q96HA9 ✓ ✓ ✓
PEX12 O00623 ✓ ✓ ✓
PEX13 Q92968 ✓ ✓ ✓
PEX14 O75381 ✓ ✓ ✓
PEX16 Q9Y5Y5 ✓ ✓ ✓
PEX19 P40855 ✓ ✓ ✓
PEX2 P28328 ✓ 58/59 ✓
PEX26 Q7Z412 ✓ ✓ ✓
PEX3 P56589 ✓ 46/47 ✓
PEX5 P50542 ✓ 117/118 ✓
PEX6 Q13608 ✓ ✓ ✓
PEX7 O00628 ✓ ✓ ✓
human MFF Q9GZY8 ✗ — —

Details

Context
EukaryotaNCBITaxon:2759
conserved eukaryotic organelle lifecycle conserved peroxin core with lineage-specific additions
Peroxisome lifecycle and matrix protein importOrganelle Lifecycleperoxisome_lifecycle
peroxisome organizationGO:0007031 peroxisomeGO:0005777
Context
EukaryotaNCBITaxon:2759
conserved eukaryotic organelle lifecycle conserved peroxin core with lineage-specific additions

Connections

A competent peroxisomal membrane is needed for matrix cargo targeting and import.
Cargo-loaded matrix import receptors dock at the importomer.
Importomer engagement creates receptor states that must be recycled.
Matrix import provides enzymes required for mature peroxisome metabolic function.
Proliferation and membrane biogenesis are coupled in peroxisome growth and maintenance.
Functional matrix import helps maintain organelle identity; import failure or unresolved ubiquitin signals can shift peroxisomes toward pexophagy and quality-control routes.
DOI:10.1038/s41467-023-44005-4
Supports cross-talk between import defects, pexophagy, and selective autophagy capacity.
Part 1: membrane protein biogenesis
Peroxisomal membrane protein biogenesisTransport Stepperoxisomal_membrane_biogenesis

Establishes an import-competent peroxisomal membrane. The conserved Pex3/Pex19 route is the central PMP targeting pathway; Pex16 or lineage-specific functional analogs support early membrane assembly and de novo biogenesis in subsets of eukaryotes.

protein import into peroxisome membraneGO:0045046
DOI:10.1007/s00418-023-02259-5
Supports Pex3/Pex19/Pex16 membrane biogenesis roles and lineage variation in PMP biogenesis.
DOI:10.1242/jcs.264075
Supports RRBP1 as a human ER-linked factor contributing to peroxisome biogenesis.
Variant set: Peroxisomal membrane protein insertion route variants by lineage-retained membrane insertion machinery (One Or More)
Pex3/Pex19 membrane protein targeting routeTransport Steppex3_pex19_pmp_route

Annotons

Pex19-family membrane protein cargo recognition
pex19_family_cargo_recognition
Participant: Family: Pex19 family
Family:
Pex19 familyPANTHER:PTHR12774
Representative Members: human PEX19UniProtKB:P40855

Function

peroxisome membrane targeting sequence bindingGO:0033328
Cargo: peroxisomal membrane protein

Locations

cytosolGO:0005829

Recognizes peroxisomal membrane protein cargo before membrane insertion.

PMID:14709540
Supports PEX19 as a peroxisomal membrane protein targeting factor.
Pex3-family membrane docking unit
pex3_family_membrane_docking
Participant: Family: Pex3 family
Family:
Pex3 familyPANTHER:PTHR28080
Representative Members: human PEX3UniProtKB:P56589

Function

membrane docking for peroxisomal membrane protein import Docking/recruitment function for Pex19-cargo complexes at the peroxisomal membrane; no exact GO MF is asserted here.
Cargo: Pex19-bound peroxisomal membrane protein

Locations

peroxisomal membraneGO:0005778

Provides a membrane-localized docking point for Pex19-mediated cargo delivery.

PMID:15007061
Supports PEX3 involvement in class I peroxisomal membrane protein import.

Connections

Pex19-bound cargo is delivered to a Pex3-family membrane docking/insertion step.
Pex16-supported membrane biogenesis routeTransport Steppex16_supported_pmp_route

A lineage-retained route in which a Pex16-family membrane factor contributes to peroxisomal membrane protein targeting or membrane assembly. This variant is not asserted to be universal across all eukaryotes; fungi may use functionally related alternatives such as Pex36.

Annotons

Pex16-family membrane biogenesis factor
pex16_family_membrane_biogenesis
Participant: Family: Pex16 family
Family:
Pex16 familyPANTHER:PTHR13299
Representative Members: human PEX16UniProtKB:Q9Y5Y5

Function

peroxisomal membrane assembly factor Membrane biogenesis role that helps establish or maintain a competent peroxisomal membrane.

Locations

peroxisomal membraneGO:0005778
RRBP1-supported ER-linked membrane biogenesis routeTransport Steprrbp1_supported_er_biogenesis_route

Accessory human-cell route in which RRBP1 supports early peroxisome biogenesis, peroxisome number, and peroxisomal protein levels, probably through ER-linked stabilization or insertion steps.

Context
human and metazoan cells where RRBP1 is retained
endoplasmic reticulumGO:0005783

Annotons

RRBP1 ER-linked peroxisome biogenesis support
rrbp1_er_linked_biogenesis_support
Participant: Gene Product: RRBP1
Gene Product:
RRBP1 Ribosome-binding protein 1, used here as an accessory representative rather than a conserved peroxin family.

Function

ER-linked support for early peroxisome biogenesis Supports peroxisome number and peroxisomal protein abundance in human cells; the precise molecular activity is not asserted here.

Locations

endoplasmic reticulumGO:0005783
DOI:10.1242/jcs.264075
Supports RRBP1 as a factor maintaining peroxisome biogenesis in human cells.
Part 2: matrix protein targeting
Matrix protein cargo targetingTransport Stepmatrix_cargo_targeting
protein import into peroxisome matrixGO:0016558
Variant set: Matrix targeting signal repertoire variants by targeting signal repertoire (One Or More)
PTS1-dependent cargo targetingTransport Steppts1_targeting_variant

Annotons

Pex5-family PTS1 cargo recognition
pex5_family_pts1_binding
Participant: Family: Pex5 family
Family:
Pex5 familyPANTHER:PTHR10130
Representative Members: human PEX5UniProtKB:P50542

Function

peroxisome matrix targeting signal-1 bindingGO:0005052
Cargo: PTS1-containing peroxisomal matrix protein

Locations

cytosolGO:0005829

Recognizes PTS1-containing matrix cargo.

PTS2-dependent cargo targetingTransport Steppts2_targeting_variant

PTS2 import is a conserved route in many eukaryotes but can be lost, reduced, or implemented with different co-receptor logic in particular lineages; fungi often use Pex20 or Pex18/Pex21-like co-receptors, and some lineages have condition-specific Pex5-like receptor paralogs.

Annotons

Pex7-family PTS2 cargo recognition
pex7_family_pts2_binding
Participant: Family: Pex7 family
Family:
Pex7 familyPANTHER:PTHR46027
Representative Members: human PEX7UniProtKB:O00628

Function

peroxisome matrix targeting signal-2 bindingGO:0005053
Cargo: PTS2-containing peroxisomal matrix protein

Locations

cytosolGO:0005829

Recognizes PTS2-containing matrix cargo.

Part 3: docking and translocation
Matrix protein docking and translocationProtein Complexmatrix_importomer

Narrowly represents receptor docking and matrix cargo translocation at the peroxisomal membrane. The downstream RING ligase and AAA+ extraction machinery are modeled in the receptor-recycling part, because current reviews often distinguish a docking/translocation importomer from an export/recycling module.

peroxisomal importomer complexGO:1990429 protein import into peroxisome matrix, dockingGO:0016560 protein import into peroxisome matrix, translocationGO:0016561

Annotons

Conserved peroxisomal importomer active units
conserved_importomer_active_units
Participant: Protein Complex: conserved peroxisomal importomer
Protein Complex:
conserved peroxisomal importomerGO:1990429
Active units:
Pex13-family docking unit
Participant: Family: Pex13 family
Family:
Pex13 familyPANTHER:PTHR19332
Representative Members: human PEX13UniProtKB:Q92968
Role: receptor docking and proposed PEX13/YG-repeat conduit scaffold
DOI:10.1016/j.tcb.2023.08.005
Supports the PEX13/YG-repeat meshwork and dual-topology conduit model.
DOI:10.1038/s41467-024-47605-w
Supports PEX13 SH3-domain interactions with PEX5 and PEX14 motifs.
Current models propose a dual-topology PEX13 conduit containing a YG-repeat meshwork, conceptually analogous to nucleoporin FG-repeat selectivity barriers.
Pex14-family docking pore unit
Participant: Family: Pex14 family
Family:
Pex14 familyPANTHER:PTHR23058
Representative Members: human PEX14UniProtKB:O75381
Role: receptor docking and matrix cargo translocation interface

Function

receptor-coupled matrix cargo docking and translocation Conserved docking/translocation activity coupling receptor engagement and matrix cargo passage. Receptor ubiquitination is represented downstream as the export/recycling module.

Locations

peroxisomal membraneGO:0005778
PMID:28765278
Supports the importomer as a docking/translocation module.
DOI:10.1016/j.tcb.2023.08.005
Supports PEX13/PEX14-centered docking/translocation and the current PEX13 conduit model.
DOI:10.1038/s41467-024-47605-w
Supports modulation of peroxisomal import by PEX13 SH3-domain interactions.
Variant set: Regulatory inputs to PEX14/PEX13-dependent import by regulatory control of docking or translocation (Zero Or More)
RNF146-TNKS/2 regulation of PEX14-dependent importRegulatory Steprnf146_tnks_pex14_regulatory_variant

Mammalian regulatory axis linking Wnt-associated PARylation machinery to peroxisome import. The module records this as a regulatory variant rather than part of the conserved import core.

Annotons

RNF146-TNKS/2 PEX14 import control
rnf146_tnks_pex14_import_control
Participant: Any Participant: RNF146-TNKS/2 regulatory axis
RNF146-TNKS/2 regulatory axis

Function

PARylation-linked regulation of PEX14-dependent matrix import
Targets: PEX14-dependent matrix import
DOI:10.1083/jcb.202312069
Supports RNF146 and TNKS/2 as regulators linking Wnt signaling to peroxisome import through PEX14.
Part 4: receptor ubiquitination and recycling
Matrix import receptor ubiquitination and recyclingTransport Stepmatrix_receptor_recycling

Export/recycling half of the matrix import cycle. Cargo release is followed by receptor monoubiquitination, ATP-dependent extraction by the PEX1/PEX6 motor, and deubiquitination/reuse; this supplies directionality to net matrix protein accumulation.

protein import into peroxisome matrix, receptor recyclingGO:0016562

Connections

Receptor monoubiquitination marks the import receptor for ATP-dependent extraction.
Part 1: receptor monoubiquitination
Matrix import receptor monoubiquitinationRegulatory Stepreceptor_monoubiquitination
protein monoubiquitinationGO:0006513

E2 logic differs by lineage. Fungal systems commonly include Pex4/Pex22-like machinery, whereas metazoan implementations lack PEX4 and use alternative E2 logic.

Annotons

RING peroxin receptor ubiquitination activity
ring_peroxin_e3_activity
Participant: Protein Complex: Pex2/Pex10/Pex12 RING peroxin module
Protein Complex:
Pex2/Pex10/Pex12 RING peroxin module
Active units:
Pex2-family E3 unit
Participant: Family: Pex2 family
Family:
Pex2 familyPANTHER:PTHR48178
Representative Members: human PEX2UniProtKB:P28328
Role: RING E3 ligase unit
Pex10-family E3 unit
Participant: Family: Pex10 family
Family:
Pex10 familyPANTHER:PTHR23350
Representative Members: human PEX10UniProtKB:O60683
Role: RING E3 ligase unit
Pex12-family E3 unit
Participant: Family: Pex12 family
Family:
Pex12 familyPANTHER:PTHR12888
Representative Members: human PEX12UniProtKB:O00623
Role: RING E3 ligase unit

Function

ubiquitin-protein transferase activity toward matrix import receptorGO:0004842
Targets: matrix import receptor
DOI:10.1016/j.tcb.2023.08.005
Supports monoubiquitination-dependent receptor recycling and the exportomer model.
PMID:24662292
Supports the RING peroxin ubiquitin-ligase module in receptor ubiquitination.

Current models emphasize monoubiquitination of PEX5 on a conserved cysteine for normal recycling. Failed recycling can shift receptors or membranes toward polyubiquitin-linked proteasomal or autophagy-associated quality-control routes.

Part 2: ATP-dependent extraction
ATP-dependent receptor extractionTransport Stepreceptor_atp_dependent_extraction

Annotons

Pex1/Pex6 ATPase receptor extraction module
pex1_pex6_atpase_recycling
Participant: Protein Complex: Pex1/Pex6 receptor extraction ATPase with membrane adaptor
Protein Complex:
Pex1/Pex6 receptor extraction ATPase with membrane adaptor
Active units:
Pex1-family ATPase unit
Participant: Family: Pex1 family
Family:
Pex1 familyPANTHER:PTHR23077:SF12
Representative Members: human PEX1UniProtKB:O43933
Role: AAA ATPase extraction motor unit
Function:
ATP hydrolysis activityGO:0016887
Pex6-family ATPase unit
Participant: Family: Pex6 family
Family:
Pex6 familyPANTHER:PTHR23077:SF9
Representative Members: human PEX6UniProtKB:Q13608
Role: AAA ATPase extraction motor unit
Function:
ATP hydrolysis activityGO:0016887
Pex26-family membrane adaptor unit
Participant: Family: Pex26 family
Family:
Pex26 familyPANTHER:PTHR16262
Representative Members: human PEX26UniProtKB:Q7Z412
Role: membrane adaptor for the extraction ATPase

Function

ATP hydrolysis-coupled receptor extractionGO:0016887
Targets: ubiquitinated matrix import receptor
Source location: peroxisomal membraneGO:0005778
Destination location: cytosolGO:0005829
PMID:35768507
Supports ATP-dependent extraction of the ubiquitinated import receptor by a Pex1/Pex6 ATPase module.
DOI:10.1016/j.tcb.2023.08.005
Supports ATP-driven extraction of ubiquitinated PEX5 by the PEX1/PEX6 AAA+ motor.
Variant set: PEX1/PEX6 membrane anchor variants by lineage-specific membrane anchor for the PEX1/PEX6 extraction ATPase (Exactly One)
DOI:10.1007/s00418-023-02259-5
Supports PEX26 and Pex15 as lineage-specific membrane anchors for the PEX1/PEX6 extraction ATPase.
PEX26-anchored receptor extractionTransport Steppex26_anchored_extraction

Metazoan and some fungal implementation in which a Pex26-family membrane adaptor anchors the PEX1/PEX6 extraction ATPase at the peroxisomal membrane.

Context
metazoan lineages and some fungi
Pex15-anchored receptor extractionTransport Steppex15_anchored_extraction

Fungal implementation in which Pex15 provides the peroxisomal membrane anchor for the Pex1/Pex6 extraction ATPase.

Context
fungi with Pex15-dependent extraction
Part 5: proliferation and division
Peroxisome elongation and divisionOrganelle Lifecycleperoxisome_proliferation
peroxisome organizationGO:0007031

Annotons

Pex11-like peroxisome membrane remodeling
pex11_like_membrane_remodeling
Participant: Family: Pex11-like membrane remodeling family
Family:
Pex11-like membrane remodeling familyPANTHER:PTHR12652 Eukaryotic peroxisomal membrane factors that promote peroxisome elongation, constriction, or division; paralog copy number and naming differ by lineage. PANTHER splits these paralogs across two families that share this membrane-remodeling role: PTHR12652 (PEX11A/PEX11B) and PTHR20990 (PEX11G); the ancestral_nodes below record the IBD node for each.
Representative Members: human PEX11AUniProtKB:O75192 human PEX11BUniProtKB:O96011 human PEX11G (PANTHER family PTHR20990)UniProtKB:Q96HA9

Function

peroxisome membrane remodeling for elongation and division Membrane-shaping role that promotes peroxisome elongation and proliferation.

Locations

peroxisomal membraneGO:0005778
PMID:20826455
Supports PEX11 family involvement in peroxisome elongation and division.
DOI:10.1007/s00418-023-02259-5
Supports PEX11-family membrane remodeling and peroxisome division route variation.
Variant set: Peroxisome division route variants by fission adaptor and membrane-remodeling route (One Or More)
PEX11-FIS1-supported division routeOrganelle Lifecyclepex11_fis1_division_route

Potentially ancient route coupling PEX11-family membrane remodeling to FIS1-supported dynamin-related scission.

DOI:10.1007/s00418-023-02259-5
Supports a PEX11/FIS1-associated division route and its evolutionary interpretation.

Annotons

PEX11/FIS1/dynamin-related division unit
pex11_fis1_dynamin_division_unit
Participant: Protein Complex: PEX11-FIS1-dynamin-related peroxisome division unit
Protein Complex:
PEX11-FIS1-dynamin-related peroxisome division unit
Active units:
PEX11-family membrane remodeling unit
Participant: Family: PEX11-like membrane remodeling family
Family:
PEX11-like membrane remodeling familyPANTHER:PTHR12652
Representative Members: human PEX11AUniProtKB:O75192 human PEX11BUniProtKB:O96011
Role: membrane elongation and constriction support
FIS1-family division adaptor unit
Participant: Family: FIS1-like fission adaptor family
Family:
FIS1-like fission adaptor family
Role: dynamin-related GTPase recruitment or support
dynamin-related scission GTPase unit
Participant: Family: dynamin-related organelle scission GTPase family
Family:
dynamin-related organelle scission GTPase familyPANTHER:PTHR11566
Representative Members: human DNM1L (DRP1)UniProtKB:O00429
Role: membrane scission

Function

peroxisome membrane scission after elongation
MFF-dependent DRP1 division routeOrganelle Lifecyclemff_dependent_division_route

Metazoan route in which MFF helps recruit DRP1/DNM1L to execute scission of elongated peroxisomal membranes.

Context
metazoan lineages
DOI:10.1007/s00418-023-02259-5
Supports MFF-dependent peroxisome fission as a metazoan route.
DOI:10.26508/lsa.202402608
Supports current DRP1 imaging tools relevant to mitochondrial and peroxisomal fission dynamics.

Annotons

MFF/DRP1 peroxisome division unit
mff_drp1_division_unit
Participant: Protein Complex: MFF-DRP1 peroxisome division unit
Protein Complex:
MFF-DRP1 peroxisome division unit
Active units:
MFF-family division adaptor unit
Participant: Family: MFF-like fission adaptor family
Family:
MFF-like fission adaptor familyPANTHER:PTHR16501:SF17
Representative Members: human MFFUniProtKB:Q9GZY8
Role: DRP1 recruitment to peroxisomal membrane
DRP1/DNM1L-family scission GTPase unit
Participant: Family: DRP1/DNM1L dynamin-related GTPase family
Family:
DRP1/DNM1L dynamin-related GTPase familyPANTHER:PTHR11566:SF39
Representative Members: human DNM1L (DRP1)UniProtKB:O00429
Role: GTP-dependent membrane scission

Function

DRP1-mediated peroxisome membrane scission
Part 6: metabolic operation
Peroxisomal matrix metabolic operationBiological Processperoxisome_matrix_metabolism

Resident peroxisomal metabolism is treated as a module interface rather than a fixed universal pathway. Beta-oxidation, reactive oxygen metabolism, ether lipid metabolism, glyoxylate-cycle functions, or specialized biosynthetic pathways can be attached as lineage-, tissue-, or environment-specific submodules.

peroxisomal matrixGO:0005782
DOI:10.1186/s13062-024-00458-1
Supports tissue-specific expression and functional specialization of peroxisomal metabolism.

Recent expression meta-analysis supports keeping metabolic operation modular rather than universal: heart, liver, and other tissues can retain similar biogenesis machinery while emphasizing different peroxisomal metabolic programs.

Part 7: quality control and turnover interface (optional)
Peroxisome quality control and turnover interfaceOrganelle Lifecycleperoxisome_quality_control

Pexophagy and ubiquitin-linked peroxisome quality control regulate organelle abundance and remove import-defective or damaged peroxisomes. This is an interface to the lifecycle rather than part of the core matrix import mechanism.

pexophagyGO:0030242

Annotons

Ubiquitin-linked pexophagy signaling
ubiquitin_linked_pexophagy_interface
Participant: Any Participant: ubiquitinated peroxisomal membrane proteins or import-defective peroxisomes
ubiquitinated peroxisomal membrane proteins or import-defective peroxisomes

Function

selective autophagy signaling for peroxisome turnover
Targets: damaged or import-defective peroxisome
DOI:10.1038/s41467-023-44005-4
Supports pexophagy as a quality-control route connected to peroxisome import defects and cellular autophagy capacity.