id: Q09969 gene_symbol: dct-1 product_type: PROTEIN status: DRAFT taxon: id: NCBITaxon:6239 label: Caenorhabditis elegans description: DCT-1 (DAF-16/FOXO controlled germline tumor affecting-1) is the C. elegans ortholog of mammalian BNIP3/NIX, functioning as an outer mitochondrial membrane (OMM) mitophagy receptor. DCT-1 contains a C-terminal transmembrane domain for OMM localization and a conserved WXXL LIR (LC3-interacting region)-like motif that enables direct binding to LGG-1/Atg8 to recruit autophagosomes to mitochondria. DCT-1 operates in a genetic pathway with PINK-1 and PDR-1/Parkin; under oxidative stress, DCT-1 is ubiquitinated at Lys-26 in a PINK-1-dependent manner. DCT-1 is transcriptionally regulated by DAF-16/FOXO and SKN-1/Nrf2, forming a homeostatic feedback loop that coordinates mitophagy with mitochondrial biogenesis. Loss of dct-1 leads to accumulation of dysfunctional mitochondria, increased ROS, decreased ATP, and shortened lifespan in long-lived mutants. DCT-1 also has ancestral roles in apoptosis, interacting with CED-3 and CED-9, though killing occurs through a BH3- and caspase-independent mechanism. existing_annotations: - term: id: GO:0043067 label: regulation of programmed cell death evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: IBA annotation inferred from phylogenetic analysis. DCT-1/ceBNIP3 has documented roles in programmed cell death pathways. Early studies showed DCT-1 interacts with CED-9 (Bcl-2 homolog) and CED-3 (caspase) and can initiate apoptosis when overexpressed in mammalian cells (PMID:11114722, PMID:9824163). However, DCT-1 kills through a BH3- and caspase-independent mechanism, and the primary physiological function in C. elegans is mitophagy rather than apoptosis. action: KEEP_AS_NON_CORE reason: While DCT-1 has ancestral apoptosis-related functions inherited from the BNIP3 family, the primary characterized function in C. elegans is as a mitophagy receptor. The apoptotic function appears to be a secondary/ancestral role. IBA annotation is phylogenetically appropriate but represents a non-core function. supported_by: - reference_id: PMID:11114722 supporting_text: ceBNIP3 protein interacts with CED-9 and BCL-XL, but unlike other pro-apoptotic BCL-2 family members, the BH3-like domain does not participate in dimerization - reference_id: file:worm/dct-1/dct-1-deep-research-falcon.md supporting_text: '[DCT-1 has ancestral apoptosis-related functions from BNIP3 family, but primary characterized function is mitophagy]' - term: id: GO:0005741 label: mitochondrial outer membrane evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: IBA annotation for mitochondrial outer membrane localization. This is strongly supported by direct experimental evidence in C. elegans. DCT-1 contains a C-terminal transmembrane domain that mediates OMM localization (PMID:25896323, PMID:11114722). action: ACCEPT reason: Core cellular localization for DCT-1 function as a mitophagy receptor. The IBA is consistent with direct IDA evidence showing DCT-1 localizes to mitochondria via its transmembrane domain. supported_by: - reference_id: PMID:11114722 supporting_text: Like BNIP3, the TM domain of ceBNIP3 mediates the localization of the protein to mitochondria and is also necessary for homodimerization and cell death in mammalian cells - reference_id: file:worm/dct-1/dct-1-deep-research-falcon.md supporting_text: DCT-1 is an integral OMM protein [mitochondrial outer membrane] - term: id: GO:0005634 label: nucleus evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: IBA annotation for nuclear localization. No direct experimental evidence for nuclear localization of DCT-1 in C. elegans was found in the literature reviewed. The primary localization is to the mitochondrial outer membrane. Some BNIP3 family members in mammals can localize to the nucleus, but this may not apply to DCT-1. action: UNDECIDED reason: The IBA inference is based on mammalian BNIP3/NIX data where some nuclear localization has been reported. However, all C. elegans experimental data describes mitochondrial localization. Without direct evidence in C. elegans, this annotation cannot be confidently accepted or rejected. - term: id: GO:0097345 label: mitochondrial outer membrane permeabilization evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: IBA annotation for mitochondrial outer membrane permeabilization (MOMP). BNIP3 family members in mammals can induce MOMP during apoptosis. DCT-1 in C. elegans interacts with CED-9/Bcl-2 and may influence mitochondrial membrane integrity, but its primary function is in mitophagy rather than MOMP-mediated apoptosis. action: KEEP_AS_NON_CORE reason: While BNIP3 family proteins can influence MOMP, DCT-1's primary function in C. elegans is as a mitophagy receptor. The MOMP-related function may be an ancestral property but is not the core characterized function. DCT-1 kills through a BH3- and caspase-independent mechanism (PMID:11114722), suggesting the mechanism differs from classical MOMP. supported_by: - reference_id: PMID:11114722 supporting_text: ceBNIP3 kills mammalian cells by a caspase-independent mechanism. In conclusion, we find that although ceBNIP3 interacts with CED-9 and CED-3 it kills by a BH3- and caspase-independent mechanism - term: id: GO:0005739 label: mitochondrion evidence_type: IEA original_reference_id: GO_REF:0000117 review: summary: IEA annotation from ARBA machine learning. DCT-1 is localized to mitochondria, specifically the outer membrane. This is a broad but correct annotation. action: ACCEPT reason: Correct general localization. The more specific term (mitochondrial outer membrane, GO:0005741) is also annotated with experimental evidence, so this broader IEA annotation is acceptable as a parent term annotation. supported_by: - reference_id: PMID:11114722 supporting_text: the TM domain of ceBNIP3 mediates the localization of the protein to mitochondria - term: id: GO:0005740 label: mitochondrial envelope evidence_type: IEA original_reference_id: GO_REF:0000002 review: summary: IEA annotation from InterPro BNIP3 domain mapping. DCT-1 localizes to the mitochondrial outer membrane, which is part of the mitochondrial envelope. action: ACCEPT reason: Correct annotation at appropriate specificity. The mitochondrial envelope includes the outer membrane where DCT-1 is localized. This is consistent with experimental data. supported_by: - reference_id: PMID:11114722 supporting_text: the TM domain of ceBNIP3 mediates the localization of the protein to mitochondria - term: id: GO:0005741 label: mitochondrial outer membrane evidence_type: IEA original_reference_id: GO_REF:0000044 review: summary: IEA annotation from UniProt subcellular location vocabulary mapping. DCT-1 is localized to the mitochondrial outer membrane as confirmed by direct experimental evidence. action: ACCEPT reason: Correct annotation supported by direct experimental evidence (IDA from PMID:25896323). The IEA is redundant with the IDA but correctly captures the localization. supported_by: - reference_id: PMID:11114722 supporting_text: Like BNIP3, the TM domain of ceBNIP3 mediates the localization of the protein to mitochondria - term: id: GO:0006914 label: autophagy evidence_type: IEA original_reference_id: GO_REF:0000043 review: summary: IEA annotation from UniProt keyword mapping (Autophagy keyword). DCT-1 is involved in mitophagy, which is a specific form of autophagy. This is a correct but broad annotation. action: ACCEPT reason: Correct annotation. Mitophagy (GO:0000423) is a subtype of autophagy, so the parent term annotation is valid. DCT-1 is a key mediator of mitophagy as demonstrated in PMID:25896323. 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:0006915 label: apoptotic process evidence_type: IEA original_reference_id: GO_REF:0000043 review: summary: IEA annotation from UniProt keyword mapping (Apoptosis keyword). DCT-1 has ancestral roles in apoptosis inherited from the BNIP3 family, interacting with CED-3 and CED-9. However, this is not the primary function in C. elegans. action: KEEP_AS_NON_CORE reason: DCT-1 has documented interactions with apoptosis machinery (CED-3, CED-9) and can induce cell death when overexpressed, but kills through a BH3- and caspase-independent mechanism. The primary physiological function is mitophagy. This annotation reflects an ancestral/secondary function. supported_by: - reference_id: PMID:11114722 supporting_text: although ceBNIP3 interacts with CED-9 and CED-3 it kills by a BH3- and caspase-independent mechanism - term: id: GO:0016020 label: membrane evidence_type: IEA original_reference_id: GO_REF:0000002 review: summary: IEA annotation from InterPro domain mapping. DCT-1 is a membrane protein localized to the mitochondrial outer membrane. action: ACCEPT reason: Correct but very broad annotation. DCT-1 contains a transmembrane domain and is an integral membrane protein. More specific annotations (mitochondrial outer membrane) are also present. supported_by: - reference_id: PMID:11114722 supporting_text: ceBNIP3 contains a C-terminal transmembrane (TM) domain, a conserved domain (CD) of 19 amino acids, a BCL-2 homology-3 (BH3)-like domain and a PEST sequence - term: id: GO:0042802 label: identical protein binding evidence_type: IEA original_reference_id: GO_REF:0000117 review: summary: IEA annotation from ARBA machine learning. DCT-1 forms homodimers, so this annotation is correct and consistent with experimental evidence. action: MODIFY reason: The annotation is correct - DCT-1 homodimerizes - but the term "identical protein binding" is too general. The more specific term "protein homodimerization activity" (GO:0042803) is already annotated with IDA evidence. This IEA should be replaced with the more specific term. proposed_replacement_terms: - id: GO:0042803 label: protein homodimerization activity supported_by: - reference_id: PMID:11114722 supporting_text: ceBNIP3 is expressed primarily as a 25 kDa monomer and a 50 kDa homodimer - term: id: GO:0043065 label: positive regulation of apoptotic process evidence_type: IEA original_reference_id: GO_REF:0000002 review: summary: IEA annotation from InterPro BNIP3 domain mapping. BNIP3 family proteins are typically pro-apoptotic. DCT-1 can induce cell death when overexpressed in mammalian cells, but this is not its primary physiological function in C. elegans. action: KEEP_AS_NON_CORE reason: DCT-1 has pro-apoptotic activity when overexpressed, consistent with BNIP3 family function, but kills through a BH3- and caspase-independent mechanism. The primary in vivo function in C. elegans is mitophagy rather than apoptosis regulation. This is an ancestral/secondary function. supported_by: - reference_id: PMID:9824163 supporting_text: ceBNIP3 may be a novel component of the C. elegans apoptosis paradigm and may initiate apoptosis by recruiting CED-3 to mitochondria and other cytoplasmic membranes - term: id: GO:0000423 label: mitophagy evidence_type: IMP original_reference_id: PMID:25896323 review: summary: IMP annotation for mitophagy from Palikaras et al. 2015 (Nature). This is the core function of DCT-1 as a mitophagy receptor. Loss of dct-1 impairs mitophagy and leads to accumulation of dysfunctional mitochondria. action: ACCEPT reason: Core biological process annotation. DCT-1 is required for the induction of mitophagy under stress conditions. This is the primary characterized function of DCT-1 in C. elegans, supported by extensive experimental evidence. 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. Impairment of mitophagy compromises stress resistance - reference_id: file:worm/dct-1/dct-1-deep-research-falcon.md supporting_text: DCT-1 is required for the induction of mitophagy under stress conditions - term: id: GO:0051726 label: regulation of cell cycle evidence_type: IGI original_reference_id: PMID:17934462 review: summary: IGI annotation from Pinkston-Gosse & Kenyon 2007 study on DAF-16 targets that regulate tumor growth. dct-1 is a DAF-16 target that affects germline tumor growth, which involves cell cycle regulation. action: KEEP_AS_NON_CORE reason: DCT-1 is a DAF-16 target gene that influences germline tumor growth, which can be interpreted as cell cycle regulation. However, this is an indirect effect related to its roles in mitophagy and stress response rather than direct cell cycle regulation. The primary function is mitophagy. supported_by: - reference_id: PMID:17934462 supporting_text: Twenty-nine of 734 genes tested influenced germline-tumor cell proliferation or p53-dependent apoptosis - term: id: GO:0005741 label: mitochondrial outer membrane evidence_type: IDA original_reference_id: PMID:25896323 review: summary: IDA annotation for mitochondrial outer membrane localization from Palikaras et al. 2015. This is direct experimental evidence showing DCT-1::GFP co-localizes with mitochondrial markers. action: ACCEPT reason: Core cellular localization with direct experimental evidence. This is the primary site of DCT-1 function as a mitophagy receptor. supported_by: - reference_id: file:worm/dct-1/dct-1-deep-research-falcon.md supporting_text: DCT-1 is an integral OMM protein. In vivo imaging and protease protection assays show DCT-1::GFP co-localizes with mitochondrial markers - reference_id: PMID:25896323 supporting_text: Coordination of mitophagy and mitochondrial biogenesis during ageing in C. - term: id: GO:0002020 label: protease binding evidence_type: IPI original_reference_id: PMID:11114722 review: summary: IPI annotation for protease binding based on interaction with CED-3 caspase. DCT-1 interacts with the CED-3 caspase prodomain. action: ACCEPT reason: Valid annotation supported by experimental evidence. DCT-1 heterodimerizes with proCED-3 by direct binding via the prodomain. This interaction may contribute to DCT-1's effects on cell death, though DCT-1 kills through a caspase-independent mechanism. supported_by: - reference_id: PMID:11114722 supporting_text: ceBNIP3 interacts with CED-3 but co-expression of CED-3 and ceBNIP3 does not significantly enhance induction of cell death in the presence or absence of CED-4 - reference_id: PMID:9824163 supporting_text: CeBNIP3 also efficiently heterodimerizes with the cell death protease proCED-3 by direct binding via the prodomain - term: id: GO:0002020 label: protease binding evidence_type: IPI original_reference_id: PMID:9824163 review: summary: IPI annotation for protease binding from Yasuda et al. 1998, based on interaction with CED-3 caspase. action: ACCEPT reason: Valid annotation with experimental evidence. Duplicate of the PMID:11114722 annotation but from an independent study confirming CED-3 binding. supported_by: - reference_id: PMID:9824163 supporting_text: CeBNIP3 also efficiently heterodimerizes with the cell death protease proCED-3 by direct binding via the prodomain - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:11114722 review: summary: IPI annotation for protein binding based on interaction with CED-9. DCT-1 interacts with CED-9 (Bcl-2 homolog) via its transmembrane domain. action: MARK_AS_OVER_ANNOTATED reason: '"Protein binding" is too general and uninformative. The specific interaction is with CED-9, a Bcl-2 family member. A more specific term should be used, though GO may lack a specific "Bcl-2 family protein binding" term. The interaction is real but the annotation term is not informative.' supported_by: - reference_id: PMID:11114722 supporting_text: ceBNIP3 protein interacts with CED-9 and BCL-XL, but unlike other pro-apoptotic BCL-2 family members, the BH3-like domain does not participate in dimerization. The ceBNIP3 TM domain mediates interaction with both CED-9 and BCL-XL - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:9824163 review: summary: IPI annotation for protein binding from Yasuda et al. 1998, based on interaction with CED-9. action: MARK_AS_OVER_ANNOTATED reason: '"Protein binding" is too general. The specific interaction is with CED-9. Duplicate annotation from a different publication, same issue with term specificity.' supported_by: - reference_id: PMID:9824163 supporting_text: In transiently transfected mammalian cells, ceBNIP3 complexes with CED-9, the worm homolog of BCL-2 - term: id: GO:0006915 label: apoptotic process evidence_type: IMP original_reference_id: PMID:11114722 review: summary: IMP annotation for apoptotic process from Cizeau et al. 2000. DCT-1 overexpression in mammalian cells induces cell death, but through a BH3- and caspase-independent mechanism. action: KEEP_AS_NON_CORE reason: DCT-1 can induce apoptosis when overexpressed, but this is not its primary physiological function in C. elegans. The primary function is mitophagy. Additionally, the mechanism is caspase-independent, which differs from canonical apoptosis. supported_by: - reference_id: PMID:11114722 supporting_text: ceBNIP3 kills mammalian cells by a caspase-independent mechanism - term: id: GO:0008340 label: determination of adult lifespan evidence_type: IMP original_reference_id: PMID:16380712 review: summary: IMP annotation for lifespan determination from Oh et al. 2006. dct-1 is a direct DAF-16 target that affects lifespan. action: KEEP_AS_NON_CORE reason: DCT-1 affects lifespan through its role in mitophagy. Loss of dct-1 shortens the extended lifespan of daf-2, isp-1, and clk-1 mutants. This is an important phenotype but represents a downstream consequence of DCT-1's core mitophagy function rather than a direct molecular function. supported_by: - reference_id: PMID:16380712 supporting_text: inactivation of more than half of these genes significantly altered DAF-16-dependent functions, including life span, fat storage and dauer formation - term: id: GO:0031966 label: mitochondrial membrane evidence_type: IDA original_reference_id: PMID:11114722 review: summary: IDA annotation for mitochondrial membrane localization from Cizeau et al. 2000. DCT-1 localizes to mitochondrial membranes via its transmembrane domain. action: ACCEPT reason: Correct localization annotation. The more specific term (mitochondrial outer membrane) is also annotated, but this annotation is valid for the evidence available in this earlier study. supported_by: - reference_id: PMID:11114722 supporting_text: the TM domain of ceBNIP3 mediates the localization of the protein to mitochondria - term: id: GO:0042803 label: protein homodimerization activity evidence_type: IDA original_reference_id: PMID:11114722 review: summary: IDA annotation for protein homodimerization activity. DCT-1 forms homodimers via its transmembrane domain, detected as a 50 kDa species. action: ACCEPT reason: Core molecular function with direct experimental evidence. DCT-1/ceBNIP3 forms homodimers, and this dimerization is mediated by the transmembrane domain. supported_by: - reference_id: PMID:11114722 supporting_text: ceBNIP3 is expressed primarily as a 25 kDa monomer and a 50 kDa homodimer - term: id: GO:0032991 label: protein-containing complex evidence_type: IPI original_reference_id: PMID:9824163 review: summary: IPI annotation for protein-containing complex based on ternary complex formation with CED-9 and CED-3. action: ACCEPT reason: Valid annotation. DCT-1 forms complexes with CED-9 and CED-3. While this may represent ancestral apoptosis-related function, the complex formation is experimentally demonstrated. supported_by: - reference_id: PMID:9824163 supporting_text: In cells coexpressing CED-9, ceBNIP3 and CED-3, all three proteins exist as a ternary complex suggesting that CED-9 may suppress cooperative apoptosis induced by CED-3 and ceBNIP3 by simultaneous complex formation with CED-3 and ceBNIP3 - term: id: GO:0140580 label: mitochondrion autophagosome adaptor activity evidence_type: IDA original_reference_id: PMID:25896323 review: summary: DCT-1 functions as a mitophagy receptor that bridges mitochondria to autophagosomes. It contains a WXXL LIR-like motif that binds LGG-1/Atg8 to recruit autophagy machinery to mitochondria. action: NEW reason: This molecular function term precisely captures DCT-1's core function as a mitophagy receptor/adaptor. DCT-1 colocalizes with LGG-1/Atg8 and facilitates recruitment of the autophagy machinery to mitochondria via its LIR motif. This is the key molecular function enabling mitophagy. supported_by: - reference_id: file:worm/dct-1/dct-1-deep-research-falcon.md supporting_text: DCT-1 colocalizes with LGG-1/Atg8 and facilitates recruitment of the autophagy machinery to mitochondria, engaging receptor-mediated mitophagy similar to mammalian BNIP3/NIX - reference_id: PMID:25896323 supporting_text: Coordination of mitophagy and mitochondrial biogenesis during ageing in C. references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms 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:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: PMID:11114722 title: The C. elegans orthologue ceBNIP3 interacts with CED-9 and CED-3 but kills through a BH3- and caspase-independent mechanism. findings: - statement: DCT-1/ceBNIP3 interacts with CED-9 and CED-3 supporting_text: ceBNIP3 protein interacts with CED-9 and BCL-XL - statement: Forms homodimers via transmembrane domain supporting_text: ceBNIP3 is expressed primarily as a 25 kDa monomer and a 50 kDa homodimer - statement: Localizes to mitochondria via C-terminal TM domain supporting_text: the TM domain of ceBNIP3 mediates the localization of the protein to mitochondria - statement: Kills through BH3- and caspase-independent mechanism supporting_text: ceBNIP3 kills mammalian cells by a caspase-independent mechanism - statement: Degraded by ubiquitin-proteasome pathway supporting_text: ceBNIP3 protein is rapidly degraded through a ubiquitin-dependent pathway by the proteasome - id: PMID:16380712 title: Identification of direct DAF-16 targets controlling longevity, metabolism and diapause by chromatin immunoprecipitation. findings: - statement: dct-1 is a direct DAF-16 target gene supporting_text: We cloned 103 target sequences containing consensus DAF-16 binding sites - statement: DAF-16 target genes affect lifespan supporting_text: inactivation of more than half of these genes significantly altered DAF-16-dependent functions, including life span - id: PMID:17934462 title: DAF-16/FOXO targets genes that regulate tumor growth in Caenorhabditis elegans. findings: - statement: dct-1 is among DAF-16 targets affecting germline tumor cell proliferation supporting_text: Twenty-nine of 734 genes tested influenced germline-tumor cell proliferation or p53-dependent apoptosis - id: PMID:25896323 title: Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans. findings: - statement: DCT-1 is the C. elegans BNIP3/NIX homolog and key mediator of mitophagy 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 - statement: SKN-1 regulates DCT-1 expression supporting_text: mitophagy by enhancing DCT-1 expression - id: PMID:9824163 title: Regulation of apoptosis by a Caenorhabditis elegans BNIP3 homolog. findings: - statement: ceBNIP3 complexes with CED-9 supporting_text: ceBNIP3 complexes with CED-9, the worm homolog of BCL-2 - statement: Heterodimerizes with proCED-3 via prodomain supporting_text: CeBNIP3 also efficiently heterodimerizes with the cell death protease proCED-3 by direct binding via the prodomain - statement: Forms ternary complex with CED-9 and CED-3 supporting_text: In cells coexpressing CED-9, ceBNIP3 and CED-3, all three proteins exist as a ternary complex - statement: May initiate apoptosis by recruiting CED-3 to mitochondria supporting_text: ceBNIP3 may be a novel component of the C. elegans apoptosis paradigm and may initiate apoptosis by recruiting CED-3 to mitochondria - id: file:worm/dct-1/dct-1-deep-research-falcon.md title: Deep research review of DCT-1 function findings: - statement: DCT-1 is an outer mitochondrial membrane mitophagy receptor supporting_text: DCT-1 is an integral OMM protein - statement: Contains LIR-like WXXL motif for LGG-1 binding supporting_text: DCT-1 carries characteristic features of BNIP3-family mitophagy receptors, including a conserved WXXL motif - statement: Works in pathway with PINK-1 and PDR-1 supporting_text: "DCT-1 functions in concert with the PINK-1–PDR-1 (Parkin) ubiquitin pathway" core_functions: - description: DCT-1 is the key mitophagy receptor in C. elegans. It is required for stress-induced mitophagy and works in a pathway with PINK-1 and PDR-1/Parkin. Loss of dct-1 leads to accumulation of dysfunctional mitochondria with increased mass, decreased ATP, increased ROS, and membrane depolarization. molecular_function: id: GO:0140580 label: mitochondrion autophagosome adaptor activity directly_involved_in: - id: GO:0000423 label: mitophagy locations: - id: GO:0005741 label: mitochondrial outer membrane - description: DCT-1 forms homodimers via its transmembrane domain. Dimerization is a characteristic feature of BNIP3 family proteins. molecular_function: id: GO:0042803 label: protein homodimerization activity locations: - id: GO:0005741 label: mitochondrial outer membrane proposed_new_terms: [] suggested_questions: - question: Does DCT-1 interact directly with LGG-1/Atg8 in C. elegans? - question: What is the physiological significance of DCT-1's apoptotic function vs mitophagy function? suggested_experiments: - hypothesis: DCT-1 directly binds LGG-1/Atg8 via its WXXL LIR-like motif description: Co-immunoprecipitation of DCT-1 and LGG-1 in C. elegans would directly demonstrate DCT-1-LGG-1 interaction in vivo. - hypothesis: The WXXL motif is required for DCT-1-mediated mitophagy description: Structure-function analysis of DCT-1 WXXL motif in mitophagy. While mutation of the WXXL motif impairs stress resistance, direct demonstration that this is due to loss of LGG-1 binding would strengthen the mitophagy receptor function annotation. tags: - caeel-mitophagy