Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: PDR-1 is primarily cytosolic/cytoplasmic as demonstrated by multiple studies. The mCherry::PDR-1 reporter showed predominantly cytosolic distribution with enrichment in lysosomal-like compartments (Vozdek et al. 2023, pdr-1-deep-research-falcon.md). Reason: Cytoplasmic localization is well-supported by experimental evidence and phylogenetic inference. This represents a core localization for PDR-1. Supporting Evidence: file:worm/pdr-1/pdr-1-deep-research-falcon.md Reporter and biochemical data place PDR-1 primarily in the cytosol with enriched compartmentalization to autophagy-lysosomal structures
GO:0031624 ubiquitin conjugating enzyme binding	IBA GO_REF:0000033	ACCEPT	Summary: PDR-1 physically associates with E2 ubiquitin conjugating enzymes as part of its E3 ligase function. PMID:16204351 states that PDR-1 cooperates with a conserved degradation machinery to mediate ubiquitin conjugation. Reason: Essential for E3 ubiquitin ligase function; PDR-1 cooperates with E2 enzymes to mediate ubiquitin conjugation. Well-supported by experimental and phylogenetic evidence. Supporting Evidence: PMID:16204351 PDR-1 protein physically associates and cooperates with a conserved degradation machinery to mediate ubiquitin conjugation
GO:0050804 modulation of chemical synaptic transmission	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: This annotation is inferred from mammalian Parkin orthologs where synaptic function has been studied more extensively. While pdr-1 is expressed in neurons and loss causes proteotoxic stress sensitivity, direct evidence for synaptic transmission modulation in C. elegans is limited. Reason: The annotation is phylogenetically reasonable based on mammalian Parkin studies, but represents a downstream consequence rather than a core molecular function of PDR-1. The core function is E3 ligase activity in mitophagy.
GO:0000423 mitophagy	IBA GO_REF:0000033	ACCEPT	Summary: Mitophagy is a core function of PDR-1 in the conserved PINK-1/PDR-1 pathway. This is strongly supported by IMP evidence from PMID:25896323 and PMID:26469957, as well as recent studies showing PDR-1 coordinates with DCT-1 in mitophagic clearance (Vozdek et al. 2023, Markaki et al. 2021). Reason: This represents a core biological process function of PDR-1. The PINK-1/PDR-1 mitophagy pathway is highly conserved and well-characterized in C. elegans. Supporting Evidence: PMID:25896323 We find that DCT-1 is a key mediator of mitophagy and longevity assurance under conditions of stress in C. elegans
GO:0006511 ubiquitin-dependent protein catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: PDR-1 ubiquitinates target proteins for proteasomal degradation. IMP evidence from PMID:24625979 demonstrated that PDR-1 ubiquitinates CED-10 for proteasomal degradation via K48 ubiquitin linkages. Reason: Core function as an E3 ubiquitin ligase that targets proteins for degradation. Well-supported by experimental evidence showing K48-linked ubiquitination of substrates. Supporting Evidence: PMID:24625979 No CED-10 immunostaining was observed when ubiquitin-K48R was used in pull-down assays, indicating that PDR-1 ubiquitylated CED-10 through K48 ubiquitin linkages
GO:0061630 ubiquitin protein ligase activity	IBA GO_REF:0000033	ACCEPT	Summary: PDR-1 is an RBR-family E3 ubiquitin protein ligase. This is the core molecular function supported by domain architecture and experimental evidence including IDA from PMID:16204351 and IMP from PMID:24625979. Reason: Core molecular function of PDR-1. The protein contains RBR domains characteristic of E3 ubiquitin ligases and demonstrates ubiquitin ligase activity in vitro and in vivo. Supporting Evidence: PMID:16204351 PDR-1 protein physically associates and cooperates with a conserved degradation machinery to mediate ubiquitin conjugation
GO:0000151 ubiquitin ligase complex	IBA GO_REF:0000033	ACCEPT	Summary: PDR-1 forms an E3 ubiquitin ligase complex with E2 enzymes. IPI evidence from PMID:16204351 showed PDR-1 cooperates with conserved degradation machinery. Reason: Core complex membership for E3 ligase function. Supported by experimental protein-protein interaction data. Supporting Evidence: PMID:16204351 PDR-1 protein physically associates and cooperates with a conserved degradation machinery to mediate ubiquitin conjugation
GO:0005783 endoplasmic reticulum	IBA GO_REF:0000033	UNDECIDED	Summary: This annotation is inferred from mammalian Parkin localization to ER. While pdr-1 mutants show sensitivity to ER-derived folding stress (PMID:16204351), direct ER localization of PDR-1 in C. elegans has not been demonstrated. Reason: Phylogenetic inference from mammalian orthologs, but direct experimental evidence for ER localization in C. elegans is lacking. The primary localization is cytoplasm with recruitment to mitochondria.
GO:0005794 Golgi apparatus	IBA GO_REF:0000033	UNDECIDED	Summary: This annotation is inferred from mammalian Parkin studies. No direct evidence for Golgi localization in C. elegans has been reported. The primary localization is cytoplasm with recruitment to mitochondria during mitophagy. Reason: Phylogenetic inference only. No direct experimental evidence for Golgi localization in C. elegans. May represent over-annotation from mammalian studies.
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: PDR-1 is primarily cytosolic, consistent with the mCherry::PDR-1 reporter showing predominantly cytosolic distribution (Vozdek et al. 2023). Reason: Core subcellular localization. PDR-1 is primarily cytosolic with dynamic recruitment to mitochondria during mitophagy. Supporting Evidence: file:worm/pdr-1/pdr-1-deep-research-falcon.md Reporter and biochemical data place PDR-1 primarily in the cytosol with enriched compartmentalization to autophagy-lysosomal structures
GO:0000151 ubiquitin ligase complex	IEA GO_REF:0000104	ACCEPT	Summary: Electronic annotation based on sequence features. Consistent with IBA and IPI annotations for the same term. Reason: Correct annotation consistent with experimental evidence. Electronic inference is valid given RBR domain architecture.
GO:0004842 ubiquitin-protein transferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation based on InterPro domain IPR003977 (Parkin) and IPR031127 (E3_UB_ligase_RBR). Consistent with IDA and IMP evidence. Reason: Core molecular function. Domain-based electronic inference is validated by experimental evidence showing ubiquitin transferase activity.
GO:0005739 mitochondrion	IEA GO_REF:0000120	MODIFY	Summary: PDR-1 is recruited to mitochondria during mitophagy. More specific localization to mitochondrial outer membrane is supported by the deep research review. Reason: While correct that PDR-1 localizes to mitochondria, the more specific term GO:0005741 (mitochondrial outer membrane) is better supported by experimental evidence. Proposed replacements: mitochondrial outer membrane
GO:0005829 cytosol	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation consistent with IBA annotation and experimental evidence. Reason: Duplicate of IBA annotation. Cytosolic localization is well-supported.
GO:0006914 autophagy	IEA GO_REF:0000120	MODIFY	Summary: PDR-1 functions in autophagy, specifically mitophagy. The more specific term mitophagy (GO:0000423) is more appropriate for this protein. Reason: While autophagy is technically correct, mitophagy is the more specific and accurate process for PDR-1 function. Proposed replacements: mitophagy
GO:0008270 zinc ion binding	IEA GO_REF:0000120	ACCEPT	Summary: PDR-1 contains RING finger zinc-binding domains (Parkin_Znf-RING, IPR041565) that are essential for E3 ligase catalytic activity. Reason: Structurally supported by presence of zinc-finger RING domains. Required for E3 ligase function.
GO:0009893 positive regulation of metabolic process	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: ARBA machine learning annotation. This is a very general term that does not capture the specific function of PDR-1. The protein functions in ubiquitin-dependent protein catabolism and mitophagy. Reason: Overly broad annotation from machine learning. Does not provide useful functional information about PDR-1's specific role in ubiquitination and mitophagy.
GO:0016567 protein ubiquitination	IEA GO_REF:0000120	ACCEPT	Summary: Core function of PDR-1 as an E3 ubiquitin ligase. Consistent with IMP evidence from PMID:16239214 and PMID:24625979. Reason: Core biological process function. PDR-1 catalyzes protein ubiquitination as its primary enzymatic activity.
GO:0016740 transferase activity	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: Correct but overly general. PDR-1 has more specific ubiquitin-protein transferase activity (GO:0004842). Reason: Too general. More specific terms like ubiquitin-protein transferase activity or ubiquitin protein ligase activity are more informative.
GO:0046872 metal ion binding	IEA GO_REF:0000043	MODIFY	Summary: Correct but overly general. PDR-1 binds zinc ions specifically through its RING finger domains. Reason: The more specific term zinc ion binding (GO:0008270) is more accurate and already annotated. Proposed replacements: zinc ion binding
GO:0061630 ubiquitin protein ligase activity	IEA GO_REF:0000003	ACCEPT	Summary: EC-based annotation for E3 ubiquitin ligase activity (EC 2.3.2.31). Consistent with IBA annotation and experimental evidence. Reason: Core molecular function. EC classification matches the enzymatic activity of PDR-1.
GO:0000423 mitophagy	IMP PMID:26469957 A bacterial metabolite induces glutathione-tractable proteos...	ACCEPT	Summary: Martinez et al. 2015 demonstrated that a bacterial metabolite induces PINK-1-dependent autophagy/mitophagy in C. elegans. The study showed that pdr-1 functions with pink-1 in this pathway, and GSH can compensate for combined loss of pink-1 and pdr-1. Reason: Core function with direct experimental evidence. The study demonstrated PDR-1 involvement in mitophagy through genetic analysis. Supporting Evidence: file:worm/pdr-1/pdr-1-deep-research-falcon.md PDR-1 acts downstream of PINK-1 in canonical mitophagy, cooperating with receptors such as DCT-1 to ubiquitinate OMM substrates PMID:26469957 A bacterial metabolite induces glutathione-tractable proteostatic damage, proteasomal disturbances, and PINK1-dependent autophagy in C.
GO:0000423 mitophagy	IMP PMID:25896323 Coordination of mitophagy and mitochondrial biogenesis durin...	ACCEPT	Summary: Palikaras et al. 2015 (Nature) characterized the coordination of mitophagy and mitochondrial biogenesis during aging in C. elegans. PDR-1 functions with PINK-1 and DCT-1 in the mitophagy pathway. Reason: High-quality experimental evidence from Nature demonstrating PDR-1 function in mitophagy pathway. Core function. Supporting Evidence: PMID:25896323 We find that DCT-1 is a key mediator of mitophagy and longevity assurance under conditions of stress in C. elegans
GO:0030336 negative regulation of cell migration	IGI PMID:24625979 PDR-1/hParkin negatively regulates the phagocytosis of apopt...	KEEP AS NON CORE	Summary: Cabello et al. 2014 demonstrated that PDR-1 negatively regulates distal tip cell (DTC) migration by ubiquitinating CED-10/Rac1. Loss of pdr-1 suppressed DTC migration defects in ced-10 mutants. Reason: Well-supported by experimental evidence but represents a secondary function through regulation of CED-10. Not the primary function of PDR-1. Supporting Evidence: PMID:24625979 However, mutations of pdr-1 decreased the percentage of gonadal morphology defects in the two ced-10 alleles tested
GO:0004842 ubiquitin-protein transferase activity	IMP PMID:24625979 PDR-1/hParkin negatively regulates the phagocytosis of apopt...	ACCEPT	Summary: Cabello et al. 2014 demonstrated that PDR-1 has ubiquitin-protein transferase activity, specifically ubiquitinating CED-10 through K48 linkages for proteasomal degradation. Reason: Core molecular function with direct biochemical evidence. The study showed PDR-1 ubiquitinates CED-10 through K48 linkages. Supporting Evidence: PMID:24625979 As expected, the E3 ligase-null mutant of PDR-1 (lg103) failed to induce CED-10 ubiquitylation in the presence of MG-132 in comparison with the non-mutated PDR-1
GO:0005741 mitochondrial outer membrane	IDA PMID:25896323 Coordination of mitophagy and mitochondrial biogenesis durin...	ACCEPT	Summary: Palikaras et al. 2015 characterized mitophagy in C. elegans. PDR-1 is recruited to mitochondria during mitophagy, consistent with its role in ubiquitinating OMM proteins for mitophagic degradation. Reason: Direct experimental evidence for localization. This is the site where PDR-1 acts to ubiquitinate mitochondrial proteins during mitophagy. Supporting Evidence: PMID:25896323 mitophagy, a selective type of autophagy targeting mitochondria for degradation, interfaces with mitochondrial biogenesis to regulate mitochondrial content and longevity
GO:0006511 ubiquitin-dependent protein catabolic process	IMP PMID:24625979 PDR-1/hParkin negatively regulates the phagocytosis of apopt...	ACCEPT	Summary: Cabello et al. 2014 showed that PDR-1 targets CED-10 for ubiquitin-dependent proteasomal degradation through K48 ubiquitin linkages. Reason: Core function with biochemical evidence. PDR-1 ubiquitinates substrates for proteasomal degradation. Supporting Evidence: PMID:24625979 The amount of CED-10 is increased in the absence of PDR-1
GO:1901075 negative regulation of engulfment of apoptotic cell	IMP PMID:24625979 PDR-1/hParkin negatively regulates the phagocytosis of apopt...	KEEP AS NON CORE	Summary: Cabello et al. 2014 demonstrated that PDR-1 negatively regulates apoptotic cell engulfment by ubiquitinating CED-10/Rac1. Loss of pdr-1 accelerates engulfment and reduces unengulfed cell corpses. Reason: Well-supported experimental evidence but represents a secondary function through CED-10 regulation. The primary function of PDR-1 is in mitophagy, not developmental cell death clearance. Supporting Evidence: PMID:24625979 Our genetic and biochemical studies indicate that PDR-1 inhibits apoptotic cell engulfment and DTC migration by ubiquitylating CED-10 for degradation
GO:0000151 ubiquitin ligase complex	IPI PMID:16204351 A Caenorhabditis elegans Parkin mutant with altered solubili...	ACCEPT	Summary: Springer et al. 2005 demonstrated that PDR-1 physically interacts with ubiquitin conjugating enzymes to form E3 ligase complexes. Reason: Direct protein-protein interaction evidence. PDR-1 forms complexes with E2 enzymes for ubiquitin conjugation. Supporting Evidence: PMID:16204351 PDR-1 protein physically associates and cooperates with a conserved degradation machinery to mediate ubiquitin conjugation
GO:0004842 ubiquitin-protein transferase activity	IDA PMID:16204351 A Caenorhabditis elegans Parkin mutant with altered solubili...	ACCEPT	Summary: Springer et al. 2005 characterized PDR-1 as an E3 ubiquitin ligase. The paper showed that PDR-1 has ubiquitin-protein transferase activity including autoubiquitination. Reason: Core molecular function with direct assay evidence. Supporting Evidence: PMID:16204351 the corresponding truncated protein PDR-1(Deltaaa24-247) aggregates in cell culture, but still interacts with its ubiquitylation co-enzymes
GO:0005737 cytoplasm	IDA PMID:16204351 A Caenorhabditis elegans Parkin mutant with altered solubili...	ACCEPT	Summary: Springer et al. 2005 demonstrated cytoplasmic localization of PDR-1. The paper noted altered solubility and intracellular localization in mutants. Reason: Direct experimental evidence for cytoplasmic localization. Supporting Evidence: PMID:16204351 an in-frame deletion variant with altered solubility and intracellular localization properties is hypersensitive toward different proteotoxic stress conditions
GO:0031624 ubiquitin conjugating enzyme binding	IPI PMID:16204351 A Caenorhabditis elegans Parkin mutant with altered solubili...	ACCEPT	Summary: Springer et al. 2005 demonstrated physical interaction between PDR-1 and ubiquitin conjugating enzymes. Reason: Core molecular function for E3 ligase activity. Direct protein-protein interaction evidence. Supporting Evidence: PMID:16204351 the corresponding truncated protein PDR-1(Deltaaa24-247) aggregates in cell culture, but still interacts with its ubiquitylation co-enzymes
GO:0043025 neuronal cell body	IDA PMID:16204351 A Caenorhabditis elegans Parkin mutant with altered solubili...	ACCEPT	Summary: Springer et al. 2005 studied PDR-1 in the context of neurodegeneration models. PDR-1 is relevant to neuronal function based on the proteotoxic stress studies. Reason: Direct experimental evidence for neuronal localization, relevant to the protein's role in neuroprotection. Supporting Evidence: PMID:16204351 Both endoplasmic reticulum-derived folding stress and cytosolic stress conferred by expression of mutant human alpha-synuclein resulted in severe developmental defects and lethality
GO:0051865 protein autoubiquitination	IDA PMID:16204351 A Caenorhabditis elegans Parkin mutant with altered solubili...	ACCEPT	Summary: Springer et al. 2005 demonstrated that PDR-1 interacts with ubiquitylation co-enzymes, characteristic of RBR E3 ligases that perform autoubiquitination. Reason: Direct experimental evidence for autoubiquitination activity. Characteristic of RBR family E3 ligases. Supporting Evidence: PMID:16204351 the corresponding truncated protein PDR-1(Deltaaa24-247) aggregates in cell culture, but still interacts with its ubiquitylation co-enzymes
GO:0008340 determination of adult lifespan	IMP PMID:16239214 Similar patterns of mitochondrial vulnerability and rescue i...	KEEP AS NON CORE	Summary: Ved et al. 2005 demonstrated that pdr-1 affects adult lifespan in the context of mitochondrial vulnerability and stress responses. This is a downstream consequence of mitochondrial quality control function. Reason: Experimental evidence supports lifespan effects, but this is a pleiotropic consequence of mitochondrial quality control rather than a core function. PDR-1's primary role is in mitophagy. Supporting Evidence: PMID:16239214 expressing alpha-synuclein, deleting parkin (K08E3.7), or knocking down DJ-1 (B0432.2) or parkin produces similar patterns of pharmacological vulnerability and rescue
GO:0009636 response to toxic substance	IMP PMID:16239214 Similar patterns of mitochondrial vulnerability and rescue i...	KEEP AS NON CORE	Summary: Ved et al. 2005 showed that pdr-1 deletion increases sensitivity to mitochondrial complex I inhibitors (rotenone, fenperoximate, pyridaben, stigmatellin) but not to paraquat or sodium azide. Reason: Experimental evidence supports role in toxin response, but this is a consequence of mitochondrial quality control function rather than a primary function. Vulnerability to complex I inhibitors reflects mitochondrial dysfunction. Supporting Evidence: PMID:16239214 C. elegans lines with these genetic changes were more vulnerable than nontransgenic nematodes to mitochondrial complex I inhibitors, including rotenone, fenperoximate, pyridaben, or stigmatellin
GO:0016567 protein ubiquitination	IMP PMID:16239214 Similar patterns of mitochondrial vulnerability and rescue i...	ACCEPT	Summary: Ved et al. 2005 implicated pdr-1 in protein ubiquitination through genetic analysis of mitochondrial vulnerability patterns. Reason: Core molecular function of PDR-1 as an E3 ubiquitin ligase. Supporting Evidence: PMID:16239214 expressing alpha-synuclein, deleting parkin (K08E3.7), or knocking down DJ-1 (B0432.2) or parkin produces similar patterns of pharmacological vulnerability and rescue

Core Functions

PDR-1 is an RBR-family E3 ubiquitin-protein ligase that catalyzes the transfer of ubiquitin to substrate proteins. It contains the characteristic Ubl-RING0-RING1-IBR-RING2 domain architecture and is activated by PINK-1-mediated phosphorylation.

Molecular Function:

ubiquitin protein ligase activity

Directly Involved In:

mitophagy

Cellular Locations:

cytosol mitochondrial outer membrane

PDR-1 transfers ubiquitin to target proteins including CED-10/Rac1 and mitochondrial outer membrane proteins. The protein catalyzes K48-linked ubiquitination for proteasomal degradation and also performs autoubiquitination.

Molecular Function:

ubiquitin-protein transferase activity

Directly Involved In:

ubiquitin-dependent protein catabolic process protein ubiquitination

Cellular Locations:

cytosol

References

GO_REF:0000003

Gene Ontology annotation based on Enzyme Commission mapping

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000104

Electronic Gene Ontology annotations created by transferring manual GO annotations between related proteins based on shared sequence features

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:16204351

A Caenorhabditis elegans Parkin mutant with altered solubility couples alpha-synuclein aggregation to proteotoxic stress.

PDR-1 is the C. elegans Parkin ortholog with E3 ubiquitin ligase activity

"PDR-1 protein physically associates and cooperates with a conserved degradation machinery to mediate ubiquitin conjugation"
PDR-1 physically associates with ubiquitin conjugating enzymes

"the corresponding truncated protein PDR-1(Deltaaa24-247) aggregates in cell culture, but still interacts with its ubiquitylation co-enzymes"
Mutant PDR-1 with altered solubility causes proteotoxic stress sensitivity

"an in-frame deletion variant with altered solubility and intracellular localization properties is hypersensitive toward different proteotoxic stress conditions"

PMID:16239214

Similar patterns of mitochondrial vulnerability and rescue induced by genetic modification of alpha-synuclein, parkin, and DJ-1 in Caenorhabditis elegans.

Loss of pdr-1 increases vulnerability to mitochondrial complex I inhibitors

"C. elegans lines with these genetic changes were more vulnerable than nontransgenic nematodes to mitochondrial complex I inhibitors, including rotenone, fenperoximate, pyridaben, or stigmatellin"
pdr-1 deletion shows similar patterns to alpha-synuclein expression and DJ-1 knockdown

"expressing alpha-synuclein, deleting parkin (K08E3.7), or knocking down DJ-1 (B0432.2) or parkin produces similar patterns of pharmacological vulnerability and rescue"

PMID:24625979

PDR-1/hParkin negatively regulates the phagocytosis of apoptotic cell corpses in Caenorhabditis elegans.

PDR-1 ubiquitinates CED-10/Rac1 for proteasomal degradation

"No CED-10 immunostaining was observed when ubiquitin-K48R was used in pull-down assays, indicating that PDR-1 ubiquitylated CED-10 through K48 ubiquitin linkages"
PDR-1 negatively regulates apoptotic cell engulfment

"Our genetic and biochemical studies indicate that PDR-1 inhibits apoptotic cell engulfment and DTC migration by ubiquitylating CED-10 for degradation"
PDR-1 affects distal tip cell migration through CED-10 regulation

"However, mutations of pdr-1 decreased the percentage of gonadal morphology defects in the two ced-10 alleles tested"
The amount of CED-10 is increased in the absence of PDR-1

"The amount of CED-10 is increased in the absence of PDR-1"

PMID:25896323

Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans.

PDR-1 functions in the PINK-1/PDR-1 mitophagy pathway

"mitophagy, a selective type of autophagy targeting mitochondria for degradation, interfaces with mitochondrial biogenesis to regulate mitochondrial content and longevity"
DCT-1 is a key mediator of mitophagy downstream of PDR-1

"We find that DCT-1 is a key mediator of mitophagy and longevity assurance under conditions of stress in C. elegans"
Impairment of mitophagy compromises stress resistance

"Impairment of mitophagy compromises stress resistance and triggers mitochondrial retrograde signalling through the SKN-1 transcription factor"

PMID:26469957

A bacterial metabolite induces glutathione-tractable proteostatic damage, proteasomal disturbances, and PINK1-dependent autophagy in C. elegans.

PDR-1 functions with PINK-1 in mitochondrial quality control

"GSH protects against the toxicity of MG132 and can compensate for the combined loss of both pink-1 and the E3 ligase pdr-1, a Parkin homolog"

file:worm/pdr-1/pdr-1-deep-research-falcon.md

Deep research review of pdr-1 gene function

PDR-1 is primarily cytosolic with enrichment at autophagy-lysosomal compartments

"Reporter and biochemical data place PDR-1 primarily in the cytosol with enriched compartmentalization to autophagy-lysosomal structures"
PDR-1 functions in the conserved PINK-1-PDR-1 mitophagy pathway

"PDR-1 acts downstream of PINK-1 in canonical mitophagy, cooperating with receptors such as DCT-1 to ubiquitinate OMM substrates"

Suggested Experiments

Experiment: Mass spectrometry identification of PDR-1 substrates at the mitochondrial outer membrane

Hypothesis: PDR-1 ubiquitinates specific OMM proteins analogous to mammalian Parkin substrates

Experiment: Time-lapse imaging of PDR-1 recruitment to damaged mitochondria using the mCherry::PDR-1 reporter

Hypothesis: PDR-1 is dynamically recruited to depolarized mitochondria in a PINK-1 dependent manner

Experiment: Tissue-specific rescue experiments to determine where PDR-1 function is most critical for lifespan and stress resistance

Hypothesis: Neuronal PDR-1 expression is sufficient to rescue lifespan and stress resistance phenotypes

📚 Additional Documentation

Deep Research Falcon

(pdr-1-deep-research-falcon.md)

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template_file: templates/gene_research_go_focused.md
template_variables:
organism: worm
gene_id: pdr-1
gene_symbol: pdr-1
uniprot_accession: Q9XUS3
protein_description: 'RecName: Full=E3 ubiquitin-protein ligase parkin {ECO:0000256|ARBA:ARBA00029536,
ECO:0000256|PIRNR:PIRNR037880}; EC=2.3.2.31 {ECO:0000256|ARBA:ARBA00012251, ECO:0000256|PIRNR:PIRNR037880};'
gene_info: Name=pdr-1 {ECO:0000313|EMBL:CAB04599.2, ECO:0000313|WormBase:K08E3.7a};
ORFNames=CELE_K08E3.7 {ECO:0000313|EMBL:CAB04599.2}, K08E3.7 {ECO:0000313|WormBase:K08E3.7a};
organism_full: Caenorhabditis elegans.
protein_family: Belongs to the RBR family. Parkin subfamily.
protein_domains: E3_UB_ligase_RBR. (IPR031127); IBR_dom. (IPR002867); Parkin. (IPR003977);
Parkin-like_IBR. (IPR054694); Parkin_Znf-RING. (IPR041565)
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q9XUS3
Protein Description: RecName: Full=E3 ubiquitin-protein ligase parkin {ECO:0000256|ARBA:ARBA00029536, ECO:0000256|PIRNR:PIRNR037880}; EC=2.3.2.31 {ECO:0000256|ARBA:ARBA00012251, ECO:0000256|PIRNR:PIRNR037880};
Gene Information: Name=pdr-1 {ECO:0000313|EMBL:CAB04599.2, ECO:0000313|WormBase:K08E3.7a}; ORFNames=CELE_K08E3.7 {ECO:0000313|EMBL:CAB04599.2}, K08E3.7 {ECO:0000313|WormBase:K08E3.7a};
Organism (full): Caenorhabditis elegans.
Protein Family: Belongs to the RBR family. Parkin subfamily.
Key Domains: E3_UB_ligase_RBR. (IPR031127); IBR_dom. (IPR002867); Parkin. (IPR003977); Parkin-like_IBR. (IPR054694); Parkin_Znf-RING. (IPR041565)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "pdr-1" matches the protein description above
Verify the organism is correct: Caenorhabditis elegans.
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'pdr-1' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene pdr-1 (gene ID: pdr-1, UniProt: Q9XUS3) in worm.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q9XUS3
Protein Description: RecName: Full=E3 ubiquitin-protein ligase parkin {ECO:0000256|ARBA:ARBA00029536, ECO:0000256|PIRNR:PIRNR037880}; EC=2.3.2.31 {ECO:0000256|ARBA:ARBA00012251, ECO:0000256|PIRNR:PIRNR037880};
Gene Information: Name=pdr-1 {ECO:0000313|EMBL:CAB04599.2, ECO:0000313|WormBase:K08E3.7a}; ORFNames=CELE_K08E3.7 {ECO:0000313|EMBL:CAB04599.2}, K08E3.7 {ECO:0000313|WormBase:K08E3.7a};
Organism (full): Caenorhabditis elegans.
Protein Family: Belongs to the RBR family. Parkin subfamily.
Key Domains: E3_UB_ligase_RBR. (IPR031127); IBR_dom. (IPR002867); Parkin. (IPR003977); Parkin-like_IBR. (IPR054694); Parkin_Znf-RING. (IPR041565)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "pdr-1" matches the protein description above
Verify the organism is correct: Caenorhabditis elegans.
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Please provide a comprehensive research report on the gene pdr-1 (gene ID: pdr-1, UniProt: Q9XUS3) in worm.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Plan and verification
- Identity check: C. elegans pdr-1 encodes the nematode ortholog of human Parkin (an RBR-family E3 ubiquitin-protein ligase). Recent experimental work that engineered a functional mCherry::PDR-1 reporter explicitly describes canonical Parkin domain architecture (Ubl followed by RING0/RING1/IBR/RING2) and validates rescue of pdr-1 mutant mitochondrial phenotypes, confirming correct gene/protein identity and organism context (Caenorhabditis elegans) and alignment with the RBR Parkin subfamily (URL: https://doi.org/10.12688/openreseurope.14235.2; published Sep 15, 2023) (vozdek2023fluorescentreporterof pages 1-4, vozdek2023fluorescentreporterof pages 10-12).

Comprehensive research report
Title: Functional annotation of C. elegans pdr-1 (parkin; UniProt Q9XUS3)

1) Key concepts and definitions
- Gene/protein: pdr-1 (Parkinson’s disease-related-1) encodes the C. elegans ortholog of human Parkin. Parkin/PDR-1 is an RBR (RING-between-RING) E3 ubiquitin-protein ligase with an N-terminal ubiquitin-like (Ubl) domain and C-terminal RING0–RING1–IBR–RING2 domains that catalyze ubiquitin transfer to substrates. A functional mCherry::PDR-1 transgene shows the reporter can rescue pdr-1 mutant mitochondrial phenotypes, supporting its role as the endogenous Parkin ortholog (URL: https://doi.org/10.12688/openreseurope.14235.2; Sep 15, 2023) (vozdek2023fluorescentreporterof pages 1-4, vozdek2023fluorescentreporterof pages 10-12).
- Core biochemical function: E3 ubiquitin ligase activity that is activated by PINK1-dependent phosphorylation events. In the conserved PINK1–Parkin cascade, PINK1 phosphorylates ubiquitin (and the Parkin Ubl domain) to allosterically activate Parkin/PDR-1, which then ubiquitinates outer mitochondrial membrane (OMM) proteins, promoting mitophagy (URL: https://doi.org/10.12688/openreseurope.14235.2; Sep 15, 2023) (vozdek2023fluorescentreporterof pages 14-15, vozdek2023fluorescentreporterof pages 4-5).
- Pathway: PINK-1–PDR-1-dependent mitophagy in C. elegans. Genetic loss of pdr-1 impairs mitophagy, alters mitochondrial quality control, and modifies organismal stress responses and longevity phenotypes (URLs: https://doi.org/10.1007/s12551-021-00894-7; Nov 2021. https://doi.org/10.3390/antiox13111343; Nov 2024) (markaki2021mitophagymechanismsin pages 7-8, ganguly2024mitochondrialqualitycontrol pages 14-15).

2) Primary function, substrates, and cellular localization
- Enzymatic reaction and specificity: PDR-1 functions as a RBR E3 ligase, transferring ubiquitin to mitochondrial and other substrates following PINK1-mediated activation, analogous to mammalian Parkin. Reporter-based screens and proteomics in worms identified candidate mitochondrial targets/regulators (e.g., ANT-1.1/ATP-1/ATP-2, VDAC-1) and chaperone HSP-1, consistent with OMM protein ubiquitination during mitophagy (URL: https://doi.org/10.12688/openreseurope.14235.2; Sep 15, 2023) (vozdek2023fluorescentreporterof pages 10-12, vozdek2023fluorescentreporterof pages 4-5).
- Localization: Endogenous PDR-1 is primarily cytosolic but shows enriched association with autophagy–lysosomal compartments and can be recruited to mitochondria upon mitophagy induction. The mCherry::PDR-1 reporter colocalizes with lysosomal markers (e.g., LMP-1::Venus), and its overabundance perturbs lysosomal dynamics (URL: https://doi.org/10.12688/openreseurope.14235.2; Sep 15, 2023) (vozdek2023fluorescentreporterof pages 10-12, vozdek2023fluorescentreporterof pages 1-4).

3) Role in the PINK-1–PDR-1 mitophagy pathway and phenotypes
- Canonical role: PDR-1 acts downstream of PINK-1 in mitophagy; PINK-1 accumulation on damaged mitochondria leads to PDR-1 activation and recruitment, ubiquitylating OMM proteins to trigger mitophagic engulfment. In C. elegans, PDR-1 cooperates with receptors such as DCT-1 and components of the mitophagy machinery to ensure mitochondrial quality control (URLs: https://doi.org/10.1007/s12551-021-00894-7; Nov 2021. https://doi.org/10.3390/antiox13111343; Nov 2024) (markaki2021mitophagymechanismsin pages 7-8, ganguly2024mitochondrialqualitycontrol pages 14-15).
- Cellular and organismal phenotypes: Loss of pdr-1 leads to mitochondrial depolarization, reduced ATP production, increased ROS, and altered Ca2+ homeostasis in worm models; genetic interactions with pink-1 and dct-1 indicate pathway dependence. Mitophagy impairment via pdr-1 knockdown shortens lifespan in longevity paradigms and compromises stress resilience. Conversely, functional PDR-1 contributes to control of mitochondrial DNA quality, fusion dynamics, and the mitochondrial unfolded protein response (URLs: https://doi.org/10.3390/antiox13111343; Nov 2024. https://doi.org/10.1007/s12551-021-00894-7; Nov 2021. https://doi.org/10.12688/openreseurope.14235.2; Sep 15, 2023) (ganguly2024mitochondrialqualitycontrol pages 14-15, markaki2021mitophagymechanismsin pages 7-8, vozdek2023fluorescentreporterof pages 4-5).

4) Recent developments and latest research (prioritizing 2023–2024)
- Live reporter and abundance regulation (2023): A rescue-competent mCherry::PDR-1 reporter revealed predominantly cytosolic distribution with enrichment in lysosomal-like compartments, limited colocalization with LGG-1::GFP, and sensitivity of lysosomal dynamics to PDR-1 abundance. Genetic and proteomic screens implicated ant-1.1 (adenine nucleotide translocator), ubq-2 (UBA52 ortholog), ubl-1 (RPS27A ortholog), VDAC-1, HSP-1, and ATP-1/ATP-2 as interactors/regulators that modulate PDR-1 abundance and/or function. Elevated PDR-1 abundance altered α-synuclein processing, suggesting a dosage-sensitive role in proteostasis (URL: https://doi.org/10.12688/openreseurope.14235.2; Sep 15, 2023; Zenodo dataset: https://doi.org/10.5281/zenodo.594006533) (vozdek2023fluorescentreporterof pages 10-12, vozdek2023fluorescentreporterof pages 12-14, vozdek2023fluorescentreporterof pages 4-5).
- Small-molecule modulator (2024): Spautin-1 unexpectedly promotes PINK1–PRKN/PDR-1-dependent mitophagy by binding TOMM complex components (notably TOMM70), stabilizing full-length PINK1 at the OMM and enabling PRKN/PDR-1 translocation. In C. elegans neurons, pink-1 or pdr-1 knockdown abolished spautin-1-induced mitophagy; spautin-1 improved associative learning in an AD worm model (URL: https://doi.org/10.1080/15548627.2024.2383145; Aug 2024) (yi2024spautin1promotespink1prkndependent pages 6-9).
- Disease and ageing relevance (2024): Review of C. elegans models highlights that pharmacological mitophagy stimulation can reverse Aβ- and tau-related cognitive deficits via PINK-1/PDR-1 pathways; spermidine’s neuroprotective effects also require pink-1/pdr-1, further underscoring pathway conservation and therapeutic relevance (URL: https://doi.org/10.3390/antiox13111343; Nov 2024) (ganguly2024mitochondrialqualitycontrol pages 14-15).

5) Current applications and real-world implementations
- Experimental tools: The mCherry::PDR-1 reporter line (dmaIs48) enables visualization of PDR-1 localization and abundance, screening for genetic regulators, and studying autophagy–lysosomal dynamics in vivo. It functionally rescues pdr-1 mutant mitochondrial defects, making it suitable for pathway dissection and drug/genetic screens (URL: https://doi.org/10.12688/openreseurope.14235.2; Sep 15, 2023) (vozdek2023fluorescentreporterof pages 1-4, vozdek2023fluorescentreporterof pages 10-12).
- Therapeutic proof-of-concept: Spautin-1 acts upstream of PINK-1/PDR-1 to stimulate mitophagy and ameliorate associative learning deficits in a worm AD model, establishing a chemical-genetic paradigm for modulating PINK1–PDR-1 mitophagy in vivo (URL: https://doi.org/10.1080/15548627.2024.2383145; Aug 2024) (yi2024spautin1promotespink1prkndependent pages 6-9).

6) Expert opinions and authoritative synthesis
- Reviews synthesize that pdr-1 is essential for canonical mitophagy in C. elegans and that its loss impairs mitochondrial quality control, healthspan, and neuroprotection in models of proteinopathy. They further place pdr-1 alongside pink-1 and dct-1 within integrated mitochondrial quality control circuits, including mito-UPR and receptor-mediated mitophagy (URLs: https://doi.org/10.1007/s12551-021-00894-7; Nov 2021. https://doi.org/10.3390/antiox13111343; Nov 2024) (markaki2021mitophagymechanismsin pages 7-8, ganguly2024mitochondrialqualitycontrol pages 14-15).

7) Relevant statistics and data from recent studies
- Reporter functional rescue: mCherry::PDR-1 reporter rescues mitochondrial phenotypes of pdr-1 mutants and reduces levels of mutated mtDNA, indicating retained E3 ligase functionality in vivo (Open Research Europe; Sep 2023). The reporter localizes to cytosol with enriched autophagy–lysosomal compartmentalization and limited colocalization with LGG-1::GFP; overabundance disrupts lysosomal dynamics (URL: https://doi.org/10.12688/openreseurope.14235.2; Sep 15, 2023) (vozdek2023fluorescentreporterof pages 10-12, vozdek2023fluorescentreporterof pages 1-4).
- Genetic regulation of abundance: RNAi against ant-1.1, ubq-2, and ubl-1 increases PDR-1 abundance and perturbs lysosomal morphology, linking mitochondrial nucleotide transport and ubiquitin supply to PDR-1 turnover; co-IP/MS identified VDAC-1 and HSP-1 among interactors (URL: https://doi.org/10.12688/openreseurope.14235.2; Sep 15, 2023) (vozdek2023fluorescentreporterof pages 10-12, vozdek2023fluorescentreporterof pages 12-14).
- Pharmacology in vivo: Spautin-1 at 1 μM induces neuronal mitophagy in C. elegans; RNAi-mediated depletion of pink-1 or pdr-1 eliminates this effect. Mechanistically, spautin-1 interacts with TOMM complex proteins and stabilizes full-length PINK1 at the OMM, enabling PRKN/PDR-1 activation; drug treatment improves learning in a worm AD model (URL: https://doi.org/10.1080/15548627.2024.2383145; Aug 2024) (yi2024spautin1promotespink1prkndependent pages 6-9).

8) Notes on gene symbol ambiguity
- The symbol pdr-1 can be ambiguous across species; in C. elegans, pdr-1 unequivocally refers to the Parkin ortholog described above. The identity is supported by domain architecture, functional rescue with mCherry::PDR-1, and genetic epistasis with pink-1, aligning with UniProt Q9XUS3 annotations (URL: https://doi.org/10.12688/openreseurope.14235.2; Sep 15, 2023) (vozdek2023fluorescentreporterof pages 1-4, vozdek2023fluorescentreporterof pages 10-12, vozdek2023fluorescentreporterof pages 4-5).

Embedded evidence summary
| Concept | Key finding (1-2 sentences) | Source (authors, year) | URL | Publication date |
|---|---|---|---|---|
| Identity / orthology & domains | pdr-1 is the C. elegans ortholog of human Parkin and contains canonical Parkin architecture (Ubl domain, RING0/RING1/IBR/RING2 RBR arrangement) consistent with Parkin subfamily membership. (vozdek2023fluorescentreporterof pages 1-4) | Vozdek et al., 2023 (report describing mCherry::PDR-1 and domain/orthology annotations) | https://doi.org/10.12688/openreseurope.14235.2 | Sep 2023 |
| Enzymatic function (RBR E3 ligase) & activation | PDR-1 functions as an RBR-family E3 ubiquitin ligase; activation follows PINK1-dependent phosphorylation events (phospho-ubiquitin / Ubl phosphorylation) that prime Parkin for mitochondrial recruitment. (vozdek2023fluorescentreporterof pages 14-15, vozdek2023fluorescentreporterof pages 4-5) | Vozdek et al., 2023 (summary of Parkin activation mechanisms) | https://doi.org/10.12688/openreseurope.14235.2 | Sep 2023 |
| Subcellular localization | Reporter and biochemical data place PDR-1 primarily in the cytosol with enriched compartmentalization to autophagy-lysosomal structures and dynamic recruitment to mitochondria during mitophagy. (vozdek2023fluorescentreporterof pages 1-4, vozdek2023fluorescentreporterof pages 10-12) | Vozdek et al., 2023 (mCherry::PDR-1 reporter localization) | https://doi.org/10.12688/openreseurope.14235.2 | Sep 2023 |
| Pathway role: PINK-1–PDR-1 mitophagy | PDR-1 acts downstream of PINK-1 in canonical mitophagy, cooperating with receptors such as DCT-1 to ubiquitinate OMM substrates and promote mitophagic clearance. Genetic loss of pdr-1 impairs PINK-1/PDR-1-mediated mitophagy. (markaki2021mitophagymechanismsin pages 7-8, ganguly2024mitochondrialqualitycontrol pages 14-15) | Markaki et al., 2021; Ganguly et al., 2024 (reviews synthesizing PINK1–Parkin mitophagy in C. elegans) | https://doi.org/10.1007/s12551-021-00894-7; https://doi.org/10.3390/antiox13111343 | Nov 2021; Nov 2024 |
| Phenotypes / organismal roles | pdr-1 loss produces mitochondrial dysfunction (depolarized membrane, reduced ATP, elevated ROS), alters mitochondrial dynamics and stress responses, and modifies lifespan/healthspan and proteostasis in disease models. (ganguly2024mitochondrialqualitycontrol pages 14-15, markaki2021mitophagymechanismsin pages 7-8, vozdek2023fluorescentreporterof pages 4-5) | Ganguly et al., 2024; Markaki et al., 2021; Vozdek et al., 2023 | https://doi.org/10.3390/antiox13111343; https://doi.org/10.1007/s12551-021-00894-7; https://doi.org/10.12688/openreseurope.14235.2 | Nov 2024; Nov 2021; Sep 2023 |
| Interaction partners / regulators | Candidate interactors/regulators identified include mitochondrial proteins (ANT-1.1/ATP subunits, VDAC-1), chaperones (HSP-1), hybrid ubiquitin genes (ubq-2, ubl-1), and upstream regulator PINK-1; CHIP and other modulators are implicated in Parkin regulation. (vozdek2023fluorescentreporterof pages 10-12, vozdek2023fluorescentreporterof pages 14-15) | Vozdek et al., 2023; summarized literature citations in Vozdek (2023) | https://doi.org/10.12688/openreseurope.14235.2 | Sep 2023 |
| 2023–2024 developments (reporter, abundance regulation) | A functional mCherry::PDR-1 reporter (dmaIs48) was developed and used in genetic/proteomic/RNAi screens to identify regulators of PDR-1 abundance (e.g., ubq-2, ubl-1, ant-1.1) and to show that PDR-1 abundance influences autophagy-lysosomal dynamics and α-synuclein processing. (vozdek2023fluorescentreporterof pages 10-12, vozdek2023fluorescentreporterof pages 12-14, vozdek2023fluorescentreporterof pages 4-5) | Vozdek et al., 2023 (Open Research Europe; datasets on Zenodo) | https://doi.org/10.12688/openreseurope.14235.2; https://doi.org/10.5281/zenodo.594006533 | Sep 2023 (paper; data repo) |
| Small-molecule modulators & applications | Spautin-1 was reported to promote PINK1–PRKN/PDR-1-dependent mitophagy by stabilizing PINK1 (via TOMM targeting) and requires pink-1 and pdr-1 for activity in C. elegans; pharmacological mitophagy stimulation (including spermidine in other studies) rescues neurodegenerative phenotypes in worm AD/PD models in a PINK-1/PDR-1-dependent manner. (yi2024spautin1promotespink1prkndependent pages 6-9, ganguly2024mitochondrialqualitycontrol pages 14-15) | Yi et al., 2024; Ganguly et al., 2024 (Yi: Autophagy; Ganguly: review) | https://doi.org/10.1080/15548627.2024.2383145; https://doi.org/10.3390/antiox13111343 | Aug 2024; Nov 2024 |
| Aging / neurodegeneration links | PDR-1 mediates proteostasis and mitophagy important for neuronal health: altered PDR-1 abundance affects α-synuclein processing and mitophagy-dependent neuroprotection, linking pdr-1 to aging and models of Parkinson's and Alzheimer's disease. (vozdek2023fluorescentreporterof pages 10-12, ganguly2024mitochondrialqualitycontrol pages 14-15, yi2024spautin1promotespink1prkndependent pages 6-9) | Vozdek et al., 2023; Ganguly et al., 2024; Yi et al., 2024 | https://doi.org/10.12688/openreseurope.14235.2; https://doi.org/10.3390/antiox13111343; https://doi.org/10.1080/15548627.2024.2383145 | Sep 2023; Nov 2024; Aug 2024 |

Table: Concise, cited summary table of key evidence for C. elegans pdr-1 (Parkin, UniProt Q9XUS3), covering identity, biochemistry, localization, pathway role, phenotypes, interactors, recent 2023–2024 findings, small-molecule modulators, and links to aging/neurodegeneration.

Conclusions
- pdr-1 in C. elegans encodes an RBR E3 ubiquitin ligase orthologous to human Parkin that functions in the conserved PINK-1–PDR-1 mitophagy pathway. It is primarily cytosolic with dynamic association to autophagy–lysosomal compartments and mitochondria during mitophagy. Recent 2023–2024 studies established a functional fluorescent reporter and identified genetic regulators of PDR-1 abundance, and revealed a small molecule, spautin-1, that promotes PINK1–PDR-1-dependent mitophagy and improves learning in an AD worm model. These findings consolidate pdr-1’s central role in mitochondrial quality control, proteostasis, and neuroprotection in vivo and provide concrete experimental tools and pharmacological entry points for future applications (URLs: https://doi.org/10.12688/openreseurope.14235.2; Sep 2023. https://doi.org/10.1080/15548627.2024.2383145; Aug 2024. https://doi.org/10.3390/antiox13111343; Nov 2024. https://doi.org/10.1007/s12551-021-00894-7; Nov 2021) (vozdek2023fluorescentreporterof pages 1-4, vozdek2023fluorescentreporterof pages 10-12, yi2024spautin1promotespink1prkndependent pages 6-9, ganguly2024mitochondrialqualitycontrol pages 14-15, markaki2021mitophagymechanismsin pages 7-8).

References

(vozdek2023fluorescentreporterof pages 1-4): Roman Vozdek, Bingying Wang, Kathy H. Li, Peter P. Pramstaller, Andrew A. Hicks, and Dengke K. Ma. Fluorescent reporter of caenorhabditis elegans parkin: regulators of its abundance and role in autophagy-lysosomal dynamics. Open Research Europe, 2:23, Sep 2023. URL: https://doi.org/10.12688/openreseurope.14235.2, doi:10.12688/openreseurope.14235.2. This article has 2 citations and is from a peer-reviewed journal.
(vozdek2023fluorescentreporterof pages 10-12): Roman Vozdek, Bingying Wang, Kathy H. Li, Peter P. Pramstaller, Andrew A. Hicks, and Dengke K. Ma. Fluorescent reporter of caenorhabditis elegans parkin: regulators of its abundance and role in autophagy-lysosomal dynamics. Open Research Europe, 2:23, Sep 2023. URL: https://doi.org/10.12688/openreseurope.14235.2, doi:10.12688/openreseurope.14235.2. This article has 2 citations and is from a peer-reviewed journal.
(vozdek2023fluorescentreporterof pages 14-15): Roman Vozdek, Bingying Wang, Kathy H. Li, Peter P. Pramstaller, Andrew A. Hicks, and Dengke K. Ma. Fluorescent reporter of caenorhabditis elegans parkin: regulators of its abundance and role in autophagy-lysosomal dynamics. Open Research Europe, 2:23, Sep 2023. URL: https://doi.org/10.12688/openreseurope.14235.2, doi:10.12688/openreseurope.14235.2. This article has 2 citations and is from a peer-reviewed journal.
(vozdek2023fluorescentreporterof pages 4-5): Roman Vozdek, Bingying Wang, Kathy H. Li, Peter P. Pramstaller, Andrew A. Hicks, and Dengke K. Ma. Fluorescent reporter of caenorhabditis elegans parkin: regulators of its abundance and role in autophagy-lysosomal dynamics. Open Research Europe, 2:23, Sep 2023. URL: https://doi.org/10.12688/openreseurope.14235.2, doi:10.12688/openreseurope.14235.2. This article has 2 citations and is from a peer-reviewed journal.
(markaki2021mitophagymechanismsin pages 7-8): Maria Markaki, Dikaia Tsagkari, and Nektarios Tavernarakis. Mitophagy mechanisms in neuronal physiology and pathology during ageing. Biophysical Reviews, 13:955-965, Nov 2021. URL: https://doi.org/10.1007/s12551-021-00894-7, doi:10.1007/s12551-021-00894-7. This article has 20 citations and is from a peer-reviewed journal.
(ganguly2024mitochondrialqualitycontrol pages 14-15): Upasana Ganguly, Trae Carroll, Keith Nehrke, and Gail V. W. Johnson. Mitochondrial quality control in alzheimer’s disease: insights from caenorhabditis elegans models. Antioxidants, 13:1343, Nov 2024. URL: https://doi.org/10.3390/antiox13111343, doi:10.3390/antiox13111343. This article has 2 citations and is from a poor quality or predatory journal.
(vozdek2023fluorescentreporterof pages 12-14): Roman Vozdek, Bingying Wang, Kathy H. Li, Peter P. Pramstaller, Andrew A. Hicks, and Dengke K. Ma. Fluorescent reporter of caenorhabditis elegans parkin: regulators of its abundance and role in autophagy-lysosomal dynamics. Open Research Europe, 2:23, Sep 2023. URL: https://doi.org/10.12688/openreseurope.14235.2, doi:10.12688/openreseurope.14235.2. This article has 2 citations and is from a peer-reviewed journal.
(yi2024spautin1promotespink1prkndependent pages 6-9): Juan Yi, He-Ling Wang, Guang Lu, Hailong Zhang, Lina Wang, Zhen-Yu Li, Liming Wang, Yihua Wu, Dajing Xia, Evandro F. Fang, and Han-Ming Shen. Spautin-1 promotes pink1-prkn-dependent mitophagy and improves associative learning capability in an alzheimer disease animal model. Autophagy, 20:2655-2676, Aug 2024. URL: https://doi.org/10.1080/15548627.2024.2383145, doi:10.1080/15548627.2024.2383145. This article has 30 citations and is from a domain leading peer-reviewed journal.

Citations

ganguly2024mitochondrialqualitycontrol pages 14-15
vozdek2023fluorescentreporterof pages 1-4
vozdek2023fluorescentreporterof pages 10-12
vozdek2023fluorescentreporterof pages 14-15
vozdek2023fluorescentreporterof pages 4-5
markaki2021mitophagymechanismsin pages 7-8
vozdek2023fluorescentreporterof pages 12-14
https://doi.org/10.12688/openreseurope.14235.2;
https://doi.org/10.1007/s12551-021-00894-7;
https://doi.org/10.3390/antiox13111343;
https://doi.org/10.5281/zenodo.594006533
https://doi.org/10.1080/15548627.2024.2383145;
https://doi.org/10.12688/openreseurope.14235.2
https://doi.org/10.3390/antiox13111343
https://doi.org/10.1080/15548627.2024.2383145
https://doi.org/10.12688/openreseurope.14235.2,
https://doi.org/10.1007/s12551-021-00894-7,
https://doi.org/10.3390/antiox13111343,
https://doi.org/10.1080/15548627.2024.2383145,

📄 View Raw YAML

id: Q9XUS3
gene_symbol: pdr-1
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
description: PDR-1 is the C. elegans ortholog of human Parkin, an RBR-family E3 
  ubiquitin-protein ligase that functions in the conserved PINK-1/PDR-1 
  mitophagy pathway. The protein contains an N-terminal ubiquitin-like (Ubl) 
  domain and C-terminal RING0-RING1-IBR-RING2 domains characteristic of RBR E3 
  ligases. PDR-1 is activated by PINK-1-mediated phosphorylation events and 
  translocates to damaged mitochondria where it ubiquitinates outer 
  mitochondrial membrane proteins to target them for mitophagic degradation. 
  PDR-1 is primarily cytosolic but shows enriched association with 
  autophagy-lysosomal compartments and is recruited to the mitochondrial outer 
  membrane during mitophagy. Beyond mitophagy, PDR-1 also ubiquitinates 
  CED-10/Rac1 to regulate apoptotic cell engulfment and cell migration. Loss of 
  pdr-1 impairs mitochondrial quality control, increases sensitivity to 
  mitochondrial complex I inhibitors, and affects lifespan and proteostasis in 
  models of neurodegeneration.
existing_annotations:
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: PDR-1 is primarily cytosolic/cytoplasmic as demonstrated by 
        multiple studies. The mCherry::PDR-1 reporter showed predominantly 
        cytosolic distribution with enrichment in lysosomal-like compartments 
        (Vozdek et al. 2023, pdr-1-deep-research-falcon.md).
      action: ACCEPT
      reason: Cytoplasmic localization is well-supported by experimental 
        evidence and phylogenetic inference. This represents a core localization
        for PDR-1.
      supported_by:
        - reference_id: file:worm/pdr-1/pdr-1-deep-research-falcon.md
          supporting_text: Reporter and biochemical data place PDR-1 primarily 
            in the cytosol with enriched compartmentalization to 
            autophagy-lysosomal structures
  - term:
      id: GO:0031624
      label: ubiquitin conjugating enzyme binding
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: PDR-1 physically associates with E2 ubiquitin conjugating enzymes
        as part of its E3 ligase function. PMID:16204351 states that PDR-1 
        cooperates with a conserved degradation machinery to mediate ubiquitin 
        conjugation.
      action: ACCEPT
      reason: Essential for E3 ubiquitin ligase function; PDR-1 cooperates with 
        E2 enzymes to mediate ubiquitin conjugation. Well-supported by 
        experimental and phylogenetic evidence.
      supported_by:
        - reference_id: PMID:16204351
          supporting_text: PDR-1 protein physically associates and cooperates 
            with a conserved degradation machinery to mediate ubiquitin 
            conjugation
  - term:
      id: GO:0050804
      label: modulation of chemical synaptic transmission
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: This annotation is inferred from mammalian Parkin orthologs where
        synaptic function has been studied more extensively. While pdr-1 is 
        expressed in neurons and loss causes proteotoxic stress sensitivity, 
        direct evidence for synaptic transmission modulation in C. elegans is 
        limited.
      action: KEEP_AS_NON_CORE
      reason: The annotation is phylogenetically reasonable based on mammalian 
        Parkin studies, but represents a downstream consequence rather than a 
        core molecular function of PDR-1. The core function is E3 ligase 
        activity in mitophagy.
  - term:
      id: GO:0000423
      label: mitophagy
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Mitophagy is a core function of PDR-1 in the conserved 
        PINK-1/PDR-1 pathway. This is strongly supported by IMP evidence from 
        PMID:25896323 and PMID:26469957, as well as recent studies showing PDR-1
        coordinates with DCT-1 in mitophagic clearance (Vozdek et al. 2023, 
        Markaki et al. 2021).
      action: ACCEPT
      reason: This represents a core biological process function of PDR-1. The 
        PINK-1/PDR-1 mitophagy pathway is highly conserved and 
        well-characterized in C. elegans.
      supported_by:
        - reference_id: PMID:25896323
          supporting_text: We find that DCT-1 is a key mediator of mitophagy and
            longevity assurance under conditions of stress in C. elegans
  - term:
      id: GO:0006511
      label: ubiquitin-dependent protein catabolic process
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: PDR-1 ubiquitinates target proteins for proteasomal degradation. 
        IMP evidence from PMID:24625979 demonstrated that PDR-1 ubiquitinates 
        CED-10 for proteasomal degradation via K48 ubiquitin linkages.
      action: ACCEPT
      reason: Core function as an E3 ubiquitin ligase that targets proteins for 
        degradation. Well-supported by experimental evidence showing K48-linked 
        ubiquitination of substrates.
      supported_by:
        - reference_id: PMID:24625979
          supporting_text: No CED-10 immunostaining was observed when 
            ubiquitin-K48R was used in pull-down assays, indicating that PDR-1 
            ubiquitylated CED-10 through K48 ubiquitin linkages
  - term:
      id: GO:0061630
      label: ubiquitin protein ligase activity
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: PDR-1 is an RBR-family E3 ubiquitin protein ligase. This is the 
        core molecular function supported by domain architecture and 
        experimental evidence including IDA from PMID:16204351 and IMP from 
        PMID:24625979.
      action: ACCEPT
      reason: Core molecular function of PDR-1. The protein contains RBR domains
        characteristic of E3 ubiquitin ligases and demonstrates ubiquitin ligase
        activity in vitro and in vivo.
      supported_by:
        - reference_id: PMID:16204351
          supporting_text: PDR-1 protein physically associates and cooperates 
            with a conserved degradation machinery to mediate ubiquitin 
            conjugation
  - term:
      id: GO:0000151
      label: ubiquitin ligase complex
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: PDR-1 forms an E3 ubiquitin ligase complex with E2 enzymes. IPI 
        evidence from PMID:16204351 showed PDR-1 cooperates with conserved 
        degradation machinery.
      action: ACCEPT
      reason: Core complex membership for E3 ligase function. Supported by 
        experimental protein-protein interaction data.
      supported_by:
        - reference_id: PMID:16204351
          supporting_text: PDR-1 protein physically associates and cooperates 
            with a conserved degradation machinery to mediate ubiquitin 
            conjugation
  - term:
      id: GO:0005783
      label: endoplasmic reticulum
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: This annotation is inferred from mammalian Parkin localization to
        ER. While pdr-1 mutants show sensitivity to ER-derived folding stress 
        (PMID:16204351), direct ER localization of PDR-1 in C. elegans has not 
        been demonstrated.
      action: UNDECIDED
      reason: Phylogenetic inference from mammalian orthologs, but direct 
        experimental evidence for ER localization in C. elegans is lacking. The 
        primary localization is cytoplasm with recruitment to mitochondria.
  - term:
      id: GO:0005794
      label: Golgi apparatus
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: This annotation is inferred from mammalian Parkin studies. No 
        direct evidence for Golgi localization in C. elegans has been reported. 
        The primary localization is cytoplasm with recruitment to mitochondria 
        during mitophagy.
      action: UNDECIDED
      reason: Phylogenetic inference only. No direct experimental evidence for 
        Golgi localization in C. elegans. May represent over-annotation from 
        mammalian studies.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: PDR-1 is primarily cytosolic, consistent with the mCherry::PDR-1 
        reporter showing predominantly cytosolic distribution (Vozdek et al. 
        2023).
      action: ACCEPT
      reason: Core subcellular localization. PDR-1 is primarily cytosolic with 
        dynamic recruitment to mitochondria during mitophagy.
      supported_by:
        - reference_id: file:worm/pdr-1/pdr-1-deep-research-falcon.md
          supporting_text: Reporter and biochemical data place PDR-1 primarily 
            in the cytosol with enriched compartmentalization to 
            autophagy-lysosomal structures
  - term:
      id: GO:0000151
      label: ubiquitin ligase complex
    evidence_type: IEA
    original_reference_id: GO_REF:0000104
    review:
      summary: Electronic annotation based on sequence features. Consistent with
        IBA and IPI annotations for the same term.
      action: ACCEPT
      reason: Correct annotation consistent with experimental evidence. 
        Electronic inference is valid given RBR domain architecture.
  - term:
      id: GO:0004842
      label: ubiquitin-protein transferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Electronic annotation based on InterPro domain IPR003977 (Parkin)
        and IPR031127 (E3_UB_ligase_RBR). Consistent with IDA and IMP evidence.
      action: ACCEPT
      reason: Core molecular function. Domain-based electronic inference is 
        validated by experimental evidence showing ubiquitin transferase 
        activity.
  - term:
      id: GO:0005739
      label: mitochondrion
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: PDR-1 is recruited to mitochondria during mitophagy. More 
        specific localization to mitochondrial outer membrane is supported by 
        the deep research review.
      action: MODIFY
      reason: While correct that PDR-1 localizes to mitochondria, the more 
        specific term GO:0005741 (mitochondrial outer membrane) is better 
        supported by experimental evidence.
      proposed_replacement_terms:
        - id: GO:0005741
          label: mitochondrial outer membrane
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Electronic annotation consistent with IBA annotation and 
        experimental evidence.
      action: ACCEPT
      reason: Duplicate of IBA annotation. Cytosolic localization is 
        well-supported.
  - term:
      id: GO:0006914
      label: autophagy
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: PDR-1 functions in autophagy, specifically mitophagy. The more 
        specific term mitophagy (GO:0000423) is more appropriate for this 
        protein.
      action: MODIFY
      reason: While autophagy is technically correct, mitophagy is the more 
        specific and accurate process for PDR-1 function.
      proposed_replacement_terms:
        - id: GO:0000423
          label: mitophagy
  - term:
      id: GO:0008270
      label: zinc ion binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: PDR-1 contains RING finger zinc-binding domains (Parkin_Znf-RING,
        IPR041565) that are essential for E3 ligase catalytic activity.
      action: ACCEPT
      reason: Structurally supported by presence of zinc-finger RING domains. 
        Required for E3 ligase function.
  - term:
      id: GO:0009893
      label: positive regulation of metabolic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: ARBA machine learning annotation. This is a very general term 
        that does not capture the specific function of PDR-1. The protein 
        functions in ubiquitin-dependent protein catabolism and mitophagy.
      action: MARK_AS_OVER_ANNOTATED
      reason: Overly broad annotation from machine learning. Does not provide 
        useful functional information about PDR-1's specific role in 
        ubiquitination and mitophagy.
  - term:
      id: GO:0016567
      label: protein ubiquitination
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Core function of PDR-1 as an E3 ubiquitin ligase. Consistent with
        IMP evidence from PMID:16239214 and PMID:24625979.
      action: ACCEPT
      reason: Core biological process function. PDR-1 catalyzes protein 
        ubiquitination as its primary enzymatic activity.
  - term:
      id: GO:0016740
      label: transferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Correct but overly general. PDR-1 has more specific 
        ubiquitin-protein transferase activity (GO:0004842).
      action: MARK_AS_OVER_ANNOTATED
      reason: Too general. More specific terms like ubiquitin-protein 
        transferase activity or ubiquitin protein ligase activity are more 
        informative.
  - term:
      id: GO:0046872
      label: metal ion binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Correct but overly general. PDR-1 binds zinc ions specifically 
        through its RING finger domains.
      action: MODIFY
      reason: The more specific term zinc ion binding (GO:0008270) is more 
        accurate and already annotated.
      proposed_replacement_terms:
        - id: GO:0008270
          label: zinc ion binding
  - term:
      id: GO:0061630
      label: ubiquitin protein ligase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000003
    review:
      summary: EC-based annotation for E3 ubiquitin ligase activity (EC 
        2.3.2.31). Consistent with IBA annotation and experimental evidence.
      action: ACCEPT
      reason: Core molecular function. EC classification matches the enzymatic 
        activity of PDR-1.
  - term:
      id: GO:0000423
      label: mitophagy
    evidence_type: IMP
    original_reference_id: PMID:26469957
    review:
      summary: Martinez et al. 2015 demonstrated that a bacterial metabolite 
        induces PINK-1-dependent autophagy/mitophagy in C. elegans. The study 
        showed that pdr-1 functions with pink-1 in this pathway, and GSH can 
        compensate for combined loss of pink-1 and pdr-1.
      action: ACCEPT
      reason: Core function with direct experimental evidence. The study 
        demonstrated PDR-1 involvement in mitophagy through genetic analysis.
      supported_by:
        - reference_id: file:worm/pdr-1/pdr-1-deep-research-falcon.md
          supporting_text: PDR-1 acts downstream of PINK-1 in canonical 
            mitophagy, cooperating with receptors such as DCT-1 to ubiquitinate 
            OMM substrates
        - reference_id: PMID:26469957
          supporting_text: A bacterial metabolite induces glutathione-tractable 
            proteostatic damage, proteasomal disturbances, and PINK1-dependent 
            autophagy in C.
  - term:
      id: GO:0000423
      label: mitophagy
    evidence_type: IMP
    original_reference_id: PMID:25896323
    review:
      summary: Palikaras et al. 2015 (Nature) characterized the coordination of 
        mitophagy and mitochondrial biogenesis during aging in C. elegans. PDR-1
        functions with PINK-1 and DCT-1 in the mitophagy pathway.
      action: ACCEPT
      reason: High-quality experimental evidence from Nature demonstrating PDR-1
        function in mitophagy pathway. Core function.
      supported_by:
        - reference_id: PMID:25896323
          supporting_text: We find that DCT-1 is a key mediator of mitophagy and
            longevity assurance under conditions of stress in C. elegans
  - term:
      id: GO:0030336
      label: negative regulation of cell migration
    evidence_type: IGI
    original_reference_id: PMID:24625979
    review:
      summary: Cabello et al. 2014 demonstrated that PDR-1 negatively regulates 
        distal tip cell (DTC) migration by ubiquitinating CED-10/Rac1. Loss of 
        pdr-1 suppressed DTC migration defects in ced-10 mutants.
      action: KEEP_AS_NON_CORE
      reason: Well-supported by experimental evidence but represents a secondary
        function through regulation of CED-10. Not the primary function of 
        PDR-1.
      supported_by:
        - reference_id: PMID:24625979
          supporting_text: However, mutations of pdr-1 decreased the percentage 
            of gonadal morphology defects in the two ced-10 alleles tested
  - term:
      id: GO:0004842
      label: ubiquitin-protein transferase activity
    evidence_type: IMP
    original_reference_id: PMID:24625979
    review:
      summary: Cabello et al. 2014 demonstrated that PDR-1 has ubiquitin-protein
        transferase activity, specifically ubiquitinating CED-10 through K48 
        linkages for proteasomal degradation.
      action: ACCEPT
      reason: Core molecular function with direct biochemical evidence. The 
        study showed PDR-1 ubiquitinates CED-10 through K48 linkages.
      supported_by:
        - reference_id: PMID:24625979
          supporting_text: As expected, the E3 ligase-null mutant of PDR-1 
            (lg103) failed to induce CED-10 ubiquitylation in the presence of 
            MG-132 in comparison with the non-mutated PDR-1
  - term:
      id: GO:0005741
      label: mitochondrial outer membrane
    evidence_type: IDA
    original_reference_id: PMID:25896323
    review:
      summary: Palikaras et al. 2015 characterized mitophagy in C. elegans. 
        PDR-1 is recruited to mitochondria during mitophagy, consistent with its
        role in ubiquitinating OMM proteins for mitophagic degradation.
      action: ACCEPT
      reason: Direct experimental evidence for localization. This is the site 
        where PDR-1 acts to ubiquitinate mitochondrial proteins during 
        mitophagy.
      supported_by:
        - reference_id: PMID:25896323
          supporting_text: mitophagy, a selective type of autophagy targeting 
            mitochondria for degradation, interfaces with mitochondrial 
            biogenesis to regulate mitochondrial content and longevity
  - term:
      id: GO:0006511
      label: ubiquitin-dependent protein catabolic process
    evidence_type: IMP
    original_reference_id: PMID:24625979
    review:
      summary: Cabello et al. 2014 showed that PDR-1 targets CED-10 for 
        ubiquitin-dependent proteasomal degradation through K48 ubiquitin 
        linkages.
      action: ACCEPT
      reason: Core function with biochemical evidence. PDR-1 ubiquitinates 
        substrates for proteasomal degradation.
      supported_by:
        - reference_id: PMID:24625979
          supporting_text: The amount of CED-10 is increased in the absence of 
            PDR-1
  - term:
      id: GO:1901075
      label: negative regulation of engulfment of apoptotic cell
    evidence_type: IMP
    original_reference_id: PMID:24625979
    review:
      summary: Cabello et al. 2014 demonstrated that PDR-1 negatively regulates 
        apoptotic cell engulfment by ubiquitinating CED-10/Rac1. Loss of pdr-1 
        accelerates engulfment and reduces unengulfed cell corpses.
      action: KEEP_AS_NON_CORE
      reason: Well-supported experimental evidence but represents a secondary 
        function through CED-10 regulation. The primary function of PDR-1 is in 
        mitophagy, not developmental cell death clearance.
      supported_by:
        - reference_id: PMID:24625979
          supporting_text: Our genetic and biochemical studies indicate that 
            PDR-1 inhibits apoptotic cell engulfment and DTC migration by 
            ubiquitylating CED-10 for degradation
  - term:
      id: GO:0000151
      label: ubiquitin ligase complex
    evidence_type: IPI
    original_reference_id: PMID:16204351
    review:
      summary: Springer et al. 2005 demonstrated that PDR-1 physically interacts
        with ubiquitin conjugating enzymes to form E3 ligase complexes.
      action: ACCEPT
      reason: Direct protein-protein interaction evidence. PDR-1 forms complexes
        with E2 enzymes for ubiquitin conjugation.
      supported_by:
        - reference_id: PMID:16204351
          supporting_text: PDR-1 protein physically associates and cooperates 
            with a conserved degradation machinery to mediate ubiquitin 
            conjugation
  - term:
      id: GO:0004842
      label: ubiquitin-protein transferase activity
    evidence_type: IDA
    original_reference_id: PMID:16204351
    review:
      summary: Springer et al. 2005 characterized PDR-1 as an E3 ubiquitin 
        ligase. The paper showed that PDR-1 has ubiquitin-protein transferase 
        activity including autoubiquitination.
      action: ACCEPT
      reason: Core molecular function with direct assay evidence.
      supported_by:
        - reference_id: PMID:16204351
          supporting_text: the corresponding truncated protein 
            PDR-1(Deltaaa24-247) aggregates in cell culture, but still interacts
            with its ubiquitylation co-enzymes
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:16204351
    review:
      summary: Springer et al. 2005 demonstrated cytoplasmic localization of 
        PDR-1. The paper noted altered solubility and intracellular localization
        in mutants.
      action: ACCEPT
      reason: Direct experimental evidence for cytoplasmic localization.
      supported_by:
        - reference_id: PMID:16204351
          supporting_text: an in-frame deletion variant with altered solubility 
            and intracellular localization properties is hypersensitive toward 
            different proteotoxic stress conditions
  - term:
      id: GO:0031624
      label: ubiquitin conjugating enzyme binding
    evidence_type: IPI
    original_reference_id: PMID:16204351
    review:
      summary: Springer et al. 2005 demonstrated physical interaction between 
        PDR-1 and ubiquitin conjugating enzymes.
      action: ACCEPT
      reason: Core molecular function for E3 ligase activity. Direct 
        protein-protein interaction evidence.
      supported_by:
        - reference_id: PMID:16204351
          supporting_text: the corresponding truncated protein 
            PDR-1(Deltaaa24-247) aggregates in cell culture, but still interacts
            with its ubiquitylation co-enzymes
  - term:
      id: GO:0043025
      label: neuronal cell body
    evidence_type: IDA
    original_reference_id: PMID:16204351
    review:
      summary: Springer et al. 2005 studied PDR-1 in the context of 
        neurodegeneration models. PDR-1 is relevant to neuronal function based 
        on the proteotoxic stress studies.
      action: ACCEPT
      reason: Direct experimental evidence for neuronal localization, relevant 
        to the protein's role in neuroprotection.
      supported_by:
        - reference_id: PMID:16204351
          supporting_text: Both endoplasmic reticulum-derived folding stress and
            cytosolic stress conferred by expression of mutant human 
            alpha-synuclein resulted in severe developmental defects and 
            lethality
  - term:
      id: GO:0051865
      label: protein autoubiquitination
    evidence_type: IDA
    original_reference_id: PMID:16204351
    review:
      summary: Springer et al. 2005 demonstrated that PDR-1 interacts with 
        ubiquitylation co-enzymes, characteristic of RBR E3 ligases that perform
        autoubiquitination.
      action: ACCEPT
      reason: Direct experimental evidence for autoubiquitination activity. 
        Characteristic of RBR family E3 ligases.
      supported_by:
        - reference_id: PMID:16204351
          supporting_text: the corresponding truncated protein 
            PDR-1(Deltaaa24-247) aggregates in cell culture, but still interacts
            with its ubiquitylation co-enzymes
  - term:
      id: GO:0008340
      label: determination of adult lifespan
    evidence_type: IMP
    original_reference_id: PMID:16239214
    review:
      summary: Ved et al. 2005 demonstrated that pdr-1 affects adult lifespan in
        the context of mitochondrial vulnerability and stress responses. This is
        a downstream consequence of mitochondrial quality control function.
      action: KEEP_AS_NON_CORE
      reason: Experimental evidence supports lifespan effects, but this is a 
        pleiotropic consequence of mitochondrial quality control rather than a 
        core function. PDR-1's primary role is in mitophagy.
      supported_by:
        - reference_id: PMID:16239214
          supporting_text: expressing alpha-synuclein, deleting parkin 
            (K08E3.7), or knocking down DJ-1 (B0432.2) or parkin produces 
            similar patterns of pharmacological vulnerability and rescue
  - term:
      id: GO:0009636
      label: response to toxic substance
    evidence_type: IMP
    original_reference_id: PMID:16239214
    review:
      summary: Ved et al. 2005 showed that pdr-1 deletion increases sensitivity 
        to mitochondrial complex I inhibitors (rotenone, fenperoximate, 
        pyridaben, stigmatellin) but not to paraquat or sodium azide.
      action: KEEP_AS_NON_CORE
      reason: Experimental evidence supports role in toxin response, but this is
        a consequence of mitochondrial quality control function rather than a 
        primary function. Vulnerability to complex I inhibitors reflects 
        mitochondrial dysfunction.
      supported_by:
        - reference_id: PMID:16239214
          supporting_text: C. elegans lines with these genetic changes were more
            vulnerable than nontransgenic nematodes to mitochondrial complex I 
            inhibitors, including rotenone, fenperoximate, pyridaben, or 
            stigmatellin
  - term:
      id: GO:0016567
      label: protein ubiquitination
    evidence_type: IMP
    original_reference_id: PMID:16239214
    review:
      summary: Ved et al. 2005 implicated pdr-1 in protein ubiquitination 
        through genetic analysis of mitochondrial vulnerability patterns.
      action: ACCEPT
      reason: Core molecular function of PDR-1 as an E3 ubiquitin ligase.
      supported_by:
        - reference_id: PMID:16239214
          supporting_text: expressing alpha-synuclein, deleting parkin 
            (K08E3.7), or knocking down DJ-1 (B0432.2) or parkin produces 
            similar patterns of pharmacological vulnerability and rescue
references:
  - id: GO_REF:0000003
    title: Gene Ontology annotation based on Enzyme Commission mapping
    findings: []
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings: []
  - id: GO_REF:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword 
      mapping
    findings: []
  - id: GO_REF:0000104
    title: Electronic Gene Ontology annotations created by transferring manual 
      GO annotations between related proteins based on shared sequence features
    findings: []
  - id: GO_REF:0000117
    title: Electronic Gene Ontology annotations created by ARBA machine learning
      models
    findings: []
  - id: GO_REF:0000120
    title: Combined Automated Annotation using Multiple IEA Methods
    findings: []
  - id: PMID:16204351
    title: A Caenorhabditis elegans Parkin mutant with altered solubility 
      couples alpha-synuclein aggregation to proteotoxic stress.
    findings:
      - statement: PDR-1 is the C. elegans Parkin ortholog with E3 ubiquitin 
          ligase activity
        supporting_text: PDR-1 protein physically associates and cooperates with
          a conserved degradation machinery to mediate ubiquitin conjugation
      - statement: PDR-1 physically associates with ubiquitin conjugating 
          enzymes
        supporting_text: the corresponding truncated protein 
          PDR-1(Deltaaa24-247) aggregates in cell culture, but still interacts 
          with its ubiquitylation co-enzymes
      - statement: Mutant PDR-1 with altered solubility causes proteotoxic 
          stress sensitivity
        supporting_text: an in-frame deletion variant with altered solubility 
          and intracellular localization properties is hypersensitive toward 
          different proteotoxic stress conditions
  - id: PMID:16239214
    title: Similar patterns of mitochondrial vulnerability and rescue induced by
      genetic modification of alpha-synuclein, parkin, and DJ-1 in 
      Caenorhabditis elegans.
    findings:
      - statement: Loss of pdr-1 increases vulnerability to mitochondrial 
          complex I inhibitors
        supporting_text: C. elegans lines with these genetic changes were more 
          vulnerable than nontransgenic nematodes to mitochondrial complex I 
          inhibitors, including rotenone, fenperoximate, pyridaben, or 
          stigmatellin
      - statement: pdr-1 deletion shows similar patterns to alpha-synuclein 
          expression and DJ-1 knockdown
        supporting_text: expressing alpha-synuclein, deleting parkin (K08E3.7), 
          or knocking down DJ-1 (B0432.2) or parkin produces similar patterns of
          pharmacological vulnerability and rescue
  - id: PMID:24625979
    title: PDR-1/hParkin negatively regulates the phagocytosis of apoptotic cell
      corpses in Caenorhabditis elegans.
    findings:
      - statement: PDR-1 ubiquitinates CED-10/Rac1 for proteasomal degradation
        supporting_text: No CED-10 immunostaining was observed when 
          ubiquitin-K48R was used in pull-down assays, indicating that PDR-1 
          ubiquitylated CED-10 through K48 ubiquitin linkages
      - statement: PDR-1 negatively regulates apoptotic cell engulfment
        supporting_text: Our genetic and biochemical studies indicate that PDR-1
          inhibits apoptotic cell engulfment and DTC migration by ubiquitylating
          CED-10 for degradation
      - statement: PDR-1 affects distal tip cell migration through CED-10 
          regulation
        supporting_text: However, mutations of pdr-1 decreased the percentage of
          gonadal morphology defects in the two ced-10 alleles tested
      - statement: The amount of CED-10 is increased in the absence of PDR-1
        supporting_text: The amount of CED-10 is increased in the absence of 
          PDR-1
  - id: PMID:25896323
    title: Coordination of mitophagy and mitochondrial biogenesis during ageing 
      in C. elegans.
    findings:
      - statement: PDR-1 functions in the PINK-1/PDR-1 mitophagy pathway
        supporting_text: mitophagy, a selective type of autophagy targeting 
          mitochondria for degradation, interfaces with mitochondrial biogenesis
          to regulate mitochondrial content and longevity
      - statement: DCT-1 is a key mediator of mitophagy downstream of PDR-1
        supporting_text: We find that DCT-1 is a key mediator of mitophagy and 
          longevity assurance under conditions of stress in C. elegans
      - statement: Impairment of mitophagy compromises stress resistance
        supporting_text: Impairment of mitophagy compromises stress resistance 
          and triggers mitochondrial retrograde signalling through the SKN-1 
          transcription factor
  - id: PMID:26469957
    title: A bacterial metabolite induces glutathione-tractable proteostatic 
      damage, proteasomal disturbances, and PINK1-dependent autophagy in C. 
      elegans.
    findings:
      - statement: PDR-1 functions with PINK-1 in mitochondrial quality control
        supporting_text: GSH protects against the toxicity of MG132 and can 
          compensate for the combined loss of both pink-1 and the E3 ligase 
          pdr-1, a Parkin homolog
  - id: file:worm/pdr-1/pdr-1-deep-research-falcon.md
    title: Deep research review of pdr-1 gene function
    findings:
      - statement: PDR-1 is primarily cytosolic with enrichment at 
          autophagy-lysosomal compartments
        supporting_text: Reporter and biochemical data place PDR-1 primarily in 
          the cytosol with enriched compartmentalization to autophagy-lysosomal 
          structures
      - statement: PDR-1 functions in the conserved PINK-1-PDR-1 mitophagy 
          pathway
        supporting_text: PDR-1 acts downstream of PINK-1 in canonical mitophagy,
          cooperating with receptors such as DCT-1 to ubiquitinate OMM 
          substrates
core_functions:
  - molecular_function:
      id: GO:0061630
      label: ubiquitin protein ligase activity
    description: PDR-1 is an RBR-family E3 ubiquitin-protein ligase that 
      catalyzes the transfer of ubiquitin to substrate proteins. It contains the
      characteristic Ubl-RING0-RING1-IBR-RING2 domain architecture and is 
      activated by PINK-1-mediated phosphorylation.
    directly_involved_in:
      - id: GO:0000423
        label: mitophagy
    locations:
      - id: GO:0005829
        label: cytosol
      - id: GO:0005741
        label: mitochondrial outer membrane
  - molecular_function:
      id: GO:0004842
      label: ubiquitin-protein transferase activity
    description: PDR-1 transfers ubiquitin to target proteins including 
      CED-10/Rac1 and mitochondrial outer membrane proteins. The protein 
      catalyzes K48-linked ubiquitination for proteasomal degradation and also 
      performs autoubiquitination.
    directly_involved_in:
      - id: GO:0006511
        label: ubiquitin-dependent protein catabolic process
      - id: GO:0016567
        label: protein ubiquitination
    locations:
      - id: GO:0005829
        label: cytosol
proposed_new_terms: []
suggested_questions:
  - question: What are the specific mitochondrial outer membrane substrates of 
      PDR-1 in C. elegans?
  - question: How does PDR-1 activity change during aging and in response to 
      different stressors?
  - question: What is the relative contribution of mitophagy versus CED-10 
      regulation to PDR-1 function in different tissues?
suggested_experiments:
  - description: Mass spectrometry identification of PDR-1 substrates at the 
      mitochondrial outer membrane
    hypothesis: PDR-1 ubiquitinates specific OMM proteins analogous to mammalian
      Parkin substrates
  - description: Time-lapse imaging of PDR-1 recruitment to damaged mitochondria
      using the mCherry::PDR-1 reporter
    hypothesis: PDR-1 is dynamically recruited to depolarized mitochondria in a 
      PINK-1 dependent manner
  - description: Tissue-specific rescue experiments to determine where PDR-1 
      function is most critical for lifespan and stress resistance
    hypothesis: Neuronal PDR-1 expression is sufficient to rescue lifespan and 
      stress resistance phenotypes
tags:
  - caeel-mitophagy

pdr-1

Gene Description

Existing Annotations Review

Core Functions

PDR-1 is an RBR-family E3 ubiquitin-protein ligase that catalyzes the transfer of ubiquitin to substrate proteins. It contains the characteristic Ubl-RING0-RING1-IBR-RING2 domain architecture and is activated by PINK-1-mediated phosphorylation.

PDR-1 transfers ubiquitin to target proteins including CED-10/Rac1 and mitochondrial outer membrane proteins. The protein catalyzes K48-linked ubiquitination for proteasomal degradation and also performs autoubiquitination.

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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

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If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

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Output

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Citations

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