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