{"gene":"DELE1","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2020,"finding":"DELE1 is associated with the inner mitochondrial membrane under steady-state conditions; mitochondrial stress (e.g., membrane depolarization) activates the OMA1 protease, which cleaves DELE1; the resulting short form accumulates in the cytosol where it directly interacts with and activates the eIF2α kinase HRI, triggering the integrated stress response (ISR) and ATF4 translation.","method":"Genome-wide CRISPR interference screen, co-immunoprecipitation, subcellular fractionation, in vitro kinase assays, loss-of-function (siRNA/CRISPRi) with defined eIF2α phosphorylation and ATF4 induction readouts","journal":"Nature","confidence":"High","confidence_rationale":"Tier 2 / Strong — two independent labs simultaneously published reciprocal findings using orthogonal genome-wide screens, Co-IP, fractionation, and functional rescue; findings replicated across both studies","pmids":["32132707","32132706"],"is_preprint":false},{"year":2020,"finding":"The C-terminal portion of DELE1 is sufficient to bind and activate HRI in the cytosol; stress-induced OMA1-dependent cleavage generates a short DELE1 form that accumulates in the cytosol and engages HRI via its C-terminal region.","method":"Domain-mapping experiments, truncation constructs, Co-IP, functional ISR activation assays in haploid cells and mammalian cells","journal":"Nature","confidence":"High","confidence_rationale":"Tier 2 / Strong — independently replicated in two concurrent studies with multiple orthogonal methods including Co-IP and functional readouts","pmids":["32132706","32132707"],"is_preprint":false},{"year":2022,"finding":"DELE1 is continuously imported across both mitochondrial membranes into the matrix, surveying diverse perturbations along the import route. Proteolytic removal of N-terminal sorting signals licenses DELE1 molecules in transit for mitochondrial release and stress signaling. Import defects at the mitochondrial surface allow unprocessed DELE1 precursors to bind and activate HRI directly, without the need for OMA1-mediated cleavage. Matrix proteases PITRM1 and MPP also regulate DELE1 activation by controlling presequence processing.","method":"Genome-wide genetic screens, subcellular fractionation, import assays, mutational analysis of sorting signals, loss-of-function knockouts of PITRM1/MPP","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genome-wide genetics plus multiple orthogonal biochemical approaches in a single focused study with mechanistic validation","pmids":["35388015"],"is_preprint":false},{"year":2023,"finding":"The cryo-EM structure of the C-terminal cleavage product of human DELE1 reveals it assembles into a high-order octameric complex with D4 symmetry via two sets of hydrophobic inter-subunit interactions. Mutagenesis of key oligomerization residues disrupts octamer formation in vitro and in cells, and assembly-impaired mutants are compromised in their ability to activate HRI-dependent ISR signaling.","method":"Cryo-electron microscopy structure determination, site-directed mutagenesis, in vitro reconstitution of oligomer assembly, cell-based ISR activation assays","journal":"Nature structural & molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — cryo-EM structure combined with mutagenesis and functional validation in vitro and in cells in a single rigorous study","pmids":["37550454"],"is_preprint":false},{"year":2023,"finding":"Under iron-deficient conditions, DELE1 mitochondrial import is arrested, stabilizing DELE1 on the mitochondrial surface to activate HRI-mediated ISR. Under steady-state conditions, DELE1 is degraded by the mitochondrial matrix-resident protease LONP1 shortly after import, limiting basal signaling. Iron chelation blocks LONP1-dependent degradation by preventing complete import.","method":"Iron chelation experiments, LONP1 knockout/knockdown, DELE1 import and stability assays, flow cytometry-based cell death assays in erythroid cell models","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods including genetic ablation of LONP1, import assays, and functional ISR readouts in a single focused study","pmids":["37327776"],"is_preprint":false},{"year":2010,"finding":"DELE1 (originally called DELE) was identified as a direct binding partner of DAP3 (death-associated protein 3). Stable overexpression of DELE1 sensitizes cells to TNF-α- and TRAIL-induced apoptosis, and knockdown of DELE1 rescues cells from apoptosis by these stimuli and inhibits caspase-3, -8, and -9 activation.","method":"Yeast two-hybrid screening, co-immunoprecipitation in mammalian cells, stable overexpression, siRNA knockdown with caspase activation readouts","journal":"Apoptosis","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — yeast two-hybrid and Co-IP for binding, plus functional knockdown/overexpression with specific caspase readouts; single lab","pmids":["20563667"],"is_preprint":false},{"year":2024,"finding":"Mitochondrial protein import stress (MPIS) is an overarching stress that triggers DELE1 cleavage and HRI activation. Endogenous DELE1 can be cleaved into two forms: DELE1-S (generated under depolarizing stress) and DELE1-VS (generated only under non-depolarizing MPIS). The mitochondrial protease HtrA2 mediates DELE1 cleavage into DELE1-VS; a Parkinson's disease-associated HtrA2 mutant displays reduced DELE1 processing. OMA1 is required for DELE1 cleavage in HeLa cells but is dispensable in HEK293T cells, indicating cell-type-specific protease usage.","method":"Endogenous DELE1 detection by western blot, siRNA knockdown of OMA1 and HtrA2 in multiple cell lines, overexpression of PD-associated HtrA2 mutants, DELE1 cleavage assays","journal":"Communications biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple cell lines and multiple protease knockdowns with defined cleavage product readouts; single lab with orthogonal approaches","pmids":["38555279"],"is_preprint":false},{"year":2024,"finding":"The ISR mediated by DELE1-HRI suppresses PINK1-dependent mitophagy under non-depolarizing mitochondrial stress by positively regulating mitochondrial protein import efficiency, independent of ATF4 activation. Without ISR, increased protein synthesis overwhelms the import machinery, reducing efficiency and enabling PINK1 accumulation to trigger mitophagy.","method":"DELE1/HRI loss-of-function, PINK1 accumulation assays, protein import efficiency measurements, ATF4-independent pathway analysis","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — mechanistically defined pathway with multiple genetic knockouts but single lab, preprint only","pmids":[""],"is_preprint":true},{"year":2025,"finding":"Prohibitins (PHBs) regulate DELE1 localization at the inner mitochondrial membrane; targeting PHBs (by fluorizoline treatment or knockdown) impairs the mitochondrial protein import pre-sequence pathway and causes accumulation of DELE1 outside mitochondria, activating ISR via DELE1-HRI. OMA1 is dispensable for ISR activation following PHB targeting, distinguishing this from canonical depolarization-induced DELE1 cleavage.","method":"Fluorizoline treatment, PHB siRNA knockdown, DELE1 localization by fractionation, OMA1 knockout/knockdown, ISR activation assays in HeLa and HAP1 cells","journal":"Cell death and differentiation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple genetic and pharmacological perturbations with defined mechanistic readouts; single lab but orthogonal approaches","pmids":["41291210"],"is_preprint":false},{"year":2026,"finding":"De novo designed protein binders engage a critical oligomerization interface on DELE1, block DELE1 oligomerization in vitro while preserving DELE1's ability to bind HRI, and suppress ATF4 induction and ISR activation during mitochondrial stress in cells. A crystal structure of a representative binder confirms engagement of the oligomerization interface, validated by mutagenesis.","method":"De novo protein design, in vitro binding and oligomerization assays, crystal structure determination, mutagenesis, cell-based ISR activation (ATF4) assays, mitochondrial morphology imaging","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — crystal structure with mutagenesis and functional validation, but preprint and single lab","pmids":["41717097"],"is_preprint":true},{"year":2022,"finding":"In ovarian cancer cells, OMA1 activation leads to DELE1 cleavage and cytoplasmic interaction of cleaved DELE1 with EIF2AK1 (HRI), which cooperates with ER stress sensor EIF2AK3 to amplify the EIF2S1/ATF4 signal and promote apoptosis. PHB2/STOML2 complex regulates OMA1 protease activity upstream of DELE1.","method":"OMA1 knockdown, cisplatin treatment in cells and mouse xenograft models, western blot for DELE1 cleavage and EIF2S1/ATF4, Co-IP for DELE1-EIF2AK1 interaction","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro and in vivo models with multiple genetic and pharmacological perturbations; single lab","pmids":["35163244"],"is_preprint":false}],"current_model":"DELE1 is a mitochondrial protein that serves as the central relay of the mitochondrial integrated stress response: under steady-state conditions it is continuously imported into the matrix and rapidly degraded by LONP1, but diverse mitochondrial stresses (membrane depolarization, protein import defects, iron deficiency, inner membrane disruption) trigger OMA1-dependent (or, in some contexts, HtrA2-dependent or import-arrest-dependent) proteolytic processing of DELE1, releasing a short cytosolic fragment that oligomerizes into a D4-symmetric octamer via hydrophobic interfaces and binds/activates the eIF2α kinase HRI, which phosphorylates eIF2α to induce ATF4 and the ISR; DELE1 oligomerization is required for full HRI activation, and the pathway also cross-regulates PINK1-dependent mitophagy by maintaining mitochondrial import efficiency."},"narrative":{"mechanistic_narrative":"DELE1 is the central relay of the mitochondrial integrated stress response (ISR), coupling diverse mitochondrial perturbations to cytosolic eIF2α kinase signaling [PMID:32132707, PMID:32132706]. Under steady-state conditions DELE1 is continuously imported across both mitochondrial membranes into the matrix, where it is rapidly degraded by the LONP1 protease, limiting basal signaling; processing of its N-terminal sorting signals by matrix proteases (MPP, PITRM1) and its progression through the import route render it a sensor of import integrity [PMID:35388015, PMID:37327776]. Upon mitochondrial stress—membrane depolarization, import defects, iron deficiency, or inner-membrane perturbation—the inner-membrane protease OMA1 cleaves DELE1, generating a short C-terminal fragment that accumulates in the cytosol, binds the eIF2α kinase HRI (EIF2AK1) through its C-terminal region, and activates it to phosphorylate eIF2α and induce ATF4 [PMID:32132707, PMID:32132706]. The released C-terminal fragment self-assembles into a D4-symmetric octamer via two hydrophobic inter-subunit interfaces, and this oligomerization is required for full HRI activation [PMID:37550454]. Protease usage is stress- and cell-type-specific: HtrA2 generates an alternative cleavage product under non-depolarizing import stress, and OMA1 is dispensable in certain contexts such as prohibitin-targeted import disruption [PMID:38555279, PMID:41291210]; iron deficiency and surface import arrest can stabilize and activate DELE1 independently of OMA1 cleavage [PMID:35388015, PMID:37327776]. Beyond inducing ATF4, DELE1–HRI signaling restrains PINK1-dependent mitophagy by preserving mitochondrial import efficiency. DELE1 was first identified as a DAP3-binding protein that sensitizes cells to TNFα/TRAIL-induced, caspase-dependent apoptosis [PMID:20563667].","teleology":[{"year":2010,"claim":"Before its mitochondrial role was known, DELE1 was placed in apoptotic signaling, establishing an early functional link to programmed cell death.","evidence":"Yeast two-hybrid, Co-IP, and overexpression/knockdown with caspase activation readouts in mammalian cells","pmids":["20563667"],"confidence":"Medium","gaps":["Did not connect DELE1 to mitochondrial stress sensing or the ISR","Mechanism linking DAP3 binding to caspase activation not resolved","Single lab, no orthogonal validation of the DAP3 interaction"]},{"year":2020,"claim":"Established DELE1 as the missing relay between mitochondrial stress and the cytosolic ISR, answering how mitochondrial damage triggers eIF2α phosphorylation.","evidence":"Genome-wide CRISPRi screens, Co-IP, fractionation, and in vitro kinase/ISR assays, replicated by two concurrent studies","pmids":["32132707","32132706"],"confidence":"High","gaps":["Structural basis of HRI activation not defined","Full set of activating stresses and proteases not yet mapped"]},{"year":2020,"claim":"Mapped the activating determinant to the C-terminal cleavage product, showing the short DELE1 form is the functional HRI-engaging species.","evidence":"Truncation/domain-mapping constructs, Co-IP, and functional ISR activation assays in haploid and mammalian cells","pmids":["32132706","32132707"],"confidence":"High","gaps":["Stoichiometry of the DELE1–HRI interaction unknown at this stage","Whether the fragment acts alone or as a complex not yet addressed"]},{"year":2022,"claim":"Reframed DELE1 as a surveyor of the mitochondrial import route, explaining how import defects activate signaling without requiring OMA1 cleavage.","evidence":"Genome-wide genetic screens, import and fractionation assays, sorting-signal mutagenesis, and PITRM1/MPP knockouts","pmids":["35388015"],"confidence":"High","gaps":["How unprocessed precursors engage HRI mechanistically not detailed","Relative contributions of OMA1 vs import-arrest routes in vivo unclear"]},{"year":2022,"claim":"Extended the OMA1–DELE1–HRI axis to disease, showing it cooperates with ER stress signaling to drive apoptosis in cancer cells.","evidence":"OMA1 knockdown, cisplatin treatment in cells and xenografts, Co-IP for DELE1–EIF2AK1, and EIF2S1/ATF4 western blots","pmids":["35163244"],"confidence":"Medium","gaps":["PHB2/STOML2 regulation of OMA1 upstream of DELE1 not mechanistically dissected","Single lab; generality across tumor types untested"]},{"year":2023,"claim":"Solved the structural mechanism of activation, revealing that the cleaved fragment must oligomerize into a D4-symmetric octamer to fully activate HRI.","evidence":"Cryo-EM structure, oligomerization-interface mutagenesis, in vitro reconstitution, and cell-based ISR assays","pmids":["37550454"],"confidence":"High","gaps":["Structure of the DELE1–HRI activated complex not determined","How oligomerization converts binding into kinase activation unresolved"]},{"year":2023,"claim":"Defined LONP1-dependent degradation as the basal brake and import arrest as an OMA1-independent activation mode under iron deficiency.","evidence":"Iron chelation, LONP1 knockout/knockdown, import/stability assays, and flow-based cell death assays in erythroid models","pmids":["37327776"],"confidence":"High","gaps":["How iron status is sensed by the import machinery not defined","Physiological role in erythropoiesis in vivo not established"]},{"year":2024,"claim":"Distinguished stress-specific cleavage products and proteases, identifying HtrA2 as a non-depolarizing-stress protease with Parkinson's-disease relevance.","evidence":"Endogenous DELE1 western blots, OMA1/HtrA2 siRNA across cell lines, and PD-associated HtrA2 mutant overexpression","pmids":["38555279"],"confidence":"Medium","gaps":["Functional consequences of DELE1-S vs DELE1-VS not fully resolved","Basis for cell-type-specific OMA1 dependence unexplained"]},{"year":2024,"claim":"Uncovered an ATF4-independent output of DELE1–HRI signaling that suppresses PINK1-dependent mitophagy by maintaining import efficiency.","evidence":"DELE1/HRI loss-of-function, PINK1 accumulation and import efficiency assays (preprint)","pmids":[""],"confidence":"Medium","gaps":["Preprint, single lab, not peer-reviewed","Molecular link between eIF2α phosphorylation and import efficiency not defined"]},{"year":2025,"claim":"Implicated prohibitins in controlling DELE1 inner-membrane localization, defining another OMA1-independent route to ISR activation.","evidence":"Fluorizoline treatment, PHB knockdown, fractionation, and OMA1 knockout/ISR assays in HeLa and HAP1 cells","pmids":["41291210"],"confidence":"Medium","gaps":["How PHBs physically retain DELE1 at the inner membrane not resolved","Protease, if any, generating the active species after PHB loss unidentified"]},{"year":2026,"claim":"Demonstrated the oligomerization interface is a druggable node by designing binders that block octamer assembly and suppress ISR while sparing HRI binding.","evidence":"De novo protein design, in vitro binding/oligomerization assays, crystal structure, mutagenesis, and ATF4 ISR assays (preprint)","pmids":["41717097"],"confidence":"Medium","gaps":["Preprint, single lab","In vivo efficacy and selectivity untested"]},{"year":null,"claim":"How the diverse stress inputs, protease choices, and oligomerization state are integrated to set ISR amplitude and to balance survival versus apoptosis or mitophagy remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure of the activated DELE1 octamer–HRI complex","Determinants of cell-type-specific protease usage unknown","In vivo physiological and disease roles only partially mapped"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,1,3]},{"term_id":"GO:0140313","term_label":"molecular sequestering activity","supporting_discovery_ids":[3]}],"localization":[{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[2,4]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-8953897","term_label":"Cellular responses to stimuli","supporting_discovery_ids":[0,2]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0,1]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[5,10]}],"complexes":["DELE1 D4-symmetric octamer"],"partners":["EIF2AK1","OMA1","LONP1","HTRA2","DAP3","PITRM1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q14154","full_name":"DAP3-binding cell death enhancer 1","aliases":["DAP3-binding cell death enhancer 1, long form","DELE1(L)","Death ligand signal enhancer"],"length_aa":515,"mass_kda":55.9,"function":"Protein kinase activator that acts as a key activator of the integrated stress response (ISR) following various stresses, such as iron deficiency, mitochondrial stress or mitochondrial DNA breaks (PubMed:32132706, PubMed:32132707, PubMed:35388015, PubMed:37327776, PubMed:37550454, PubMed:37832546, PubMed:38340717). Detects impaired protein import and processing in mitochondria, activating the ISR (PubMed:35388015). May also required for the induction of death receptor-mediated apoptosis through the regulation of caspase activation (PubMed:20563667) Protein kinase activator that activates the ISR in response to iron deficiency: iron deficiency impairs mitochondrial import, promoting DELE1 localization at the mitochondrial surface, where it binds and activates EIF2AK1/HRI to trigger the ISR Protein kinase activator generated by protein cleavage in response to mitochondrial stress, which accumulates in the cytosol and specifically binds to and activates the protein kinase activity of EIF2AK1/HRI (PubMed:32132706, PubMed:32132707, PubMed:37327776, PubMed:37550454, PubMed:37832546, PubMed:38340717). It thereby activates the integrated stress response (ISR): EIF2AK1/HRI activation promotes eIF-2-alpha (EIF2S1) phosphorylation, leading to a decrease in global protein synthesis and the induction of selected genes, including the transcription factor ATF4, the master transcriptional regulator of the ISR (PubMed:32132706, PubMed:32132707, PubMed:37327776, PubMed:37550454, PubMed:37832546). Also acts as an activator of PRKN-independent mitophagy: activates the protein kinase activity of EIF2AK1/HRI in response to mitochondrial damage, promoting eIF-2-alpha (EIF2S1) phosphorylation, leading to mitochondrial localization of EIF2S1 followed by induction of mitophagy (PubMed:38340717)","subcellular_location":"Cytoplasm, cytosol","url":"https://www.uniprot.org/uniprotkb/Q14154/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DELE1","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/DELE1","total_profiled":1310},"omim":[{"mim_id":"617081","title":"OMA1 ZINC METALLOPEPTIDASE; OMA1","url":"https://www.omim.org/entry/617081"},{"mim_id":"616209","title":"MYOPATHY, ISOLATED MITOCHONDRIAL, AUTOSOMAL DOMINANT; IMMD","url":"https://www.omim.org/entry/616209"},{"mim_id":"615903","title":"COILED-COIL-HELIX-COILED-COIL-HELIX DOMAIN-CONTAINING PROTEIN 10; CHCHD10","url":"https://www.omim.org/entry/615903"},{"mim_id":"615741","title":"DAP3-BINDING CELL DEATH ENHANCER 1; DELE1","url":"https://www.omim.org/entry/615741"},{"mim_id":"614719","title":"POTASSIUM CHANNEL MODULATORY FACTOR 1; KCMF1","url":"https://www.omim.org/entry/614719"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Uncertain","locations":[{"location":"Nucleoplasm","reliability":"Uncertain"},{"location":"Golgi apparatus","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DELE1"},"hgnc":{"alias_symbol":["DELE"],"prev_symbol":["KIAA0141"]},"alphafold":{"accession":"Q14154","domains":[{"cath_id":"1.25.40.10","chopping":"242-349","consensus_level":"medium","plddt":94.3574,"start":242,"end":349},{"cath_id":"1.25.40.10","chopping":"351-435","consensus_level":"medium","plddt":93.8824,"start":351,"end":435}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q14154","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q14154-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q14154-F1-predicted_aligned_error_v6.png","plddt_mean":61.09},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DELE1","jax_strain_url":"https://www.jax.org/strain/search?query=DELE1"},"sequence":{"accession":"Q14154","fasta_url":"https://rest.uniprot.org/uniprotkb/Q14154.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q14154/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q14154"}},"corpus_meta":[{"pmid":"32132707","id":"PMC_32132707","title":"Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway.","date":"2020","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/32132707","citation_count":531,"is_preprint":false},{"pmid":"32132706","id":"PMC_32132706","title":"A pathway coordinated by DELE1 relays mitochondrial stress to the cytosol.","date":"2020","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/32132706","citation_count":402,"is_preprint":false},{"pmid":"35388015","id":"PMC_35388015","title":"DELE1 tracks perturbed protein import and processing in human mitochondria.","date":"2022","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/35388015","citation_count":80,"is_preprint":false},{"pmid":"37327776","id":"PMC_37327776","title":"A mitochondrial iron-responsive pathway regulated by DELE1.","date":"2023","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/37327776","citation_count":67,"is_preprint":false},{"pmid":"37550454","id":"PMC_37550454","title":"DELE1 oligomerization promotes integrated stress response activation.","date":"2023","source":"Nature structural & molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/37550454","citation_count":39,"is_preprint":false},{"pmid":"20563667","id":"PMC_20563667","title":"Identification of DELE, a novel DAP3-binding protein which is crucial for death receptor-mediated apoptosis induction.","date":"2010","source":"Apoptosis : an international journal on programmed cell death","url":"https://pubmed.ncbi.nlm.nih.gov/20563667","citation_count":30,"is_preprint":false},{"pmid":"35163244","id":"PMC_35163244","title":"The Mitochondrial PHB2/OMA1/DELE1 Pathway Cooperates with Endoplasmic Reticulum Stress to Facilitate the Response to Chemotherapeutics in Ovarian Cancer.","date":"2022","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/35163244","citation_count":30,"is_preprint":false},{"pmid":"36539111","id":"PMC_36539111","title":"DELE1 is protective for mitochondrial cardiomyopathy.","date":"2022","source":"Journal of molecular and cellular cardiology","url":"https://pubmed.ncbi.nlm.nih.gov/36539111","citation_count":22,"is_preprint":false},{"pmid":"38555279","id":"PMC_38555279","title":"Cytosolic retention of HtrA2 during mitochondrial protein import stress triggers the DELE1-HRI pathway.","date":"2024","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/38555279","citation_count":19,"is_preprint":false},{"pmid":"39379554","id":"PMC_39379554","title":"DELE1 maintains muscle proteostasis to promote growth and survival in mitochondrial myopathy.","date":"2024","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/39379554","citation_count":18,"is_preprint":false},{"pmid":"28655335","id":"PMC_28655335","title":"Identification of G-quadruplex structures that possess transcriptional regulating functions in the Dele and Cdc6 CpG islands.","date":"2017","source":"BMC molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/28655335","citation_count":18,"is_preprint":false},{"pmid":"38102204","id":"PMC_38102204","title":"DELE1 haploinsufficiency causes resistance to mitochondrial stress-induced apoptosis in monosomy 5/del(5q) AML.","date":"2023","source":"Leukemia","url":"https://pubmed.ncbi.nlm.nih.gov/38102204","citation_count":10,"is_preprint":false},{"pmid":"36382667","id":"PMC_36382667","title":"Death associated protein‑3 (DAP3) and DAP3 binding cell death enhancer‑1 (DELE1) in human colorectal cancer, and their impacts on clinical outcome and chemoresistance.","date":"2022","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/36382667","citation_count":9,"is_preprint":false},{"pmid":"38529505","id":"PMC_38529505","title":"DELE1 promotes translation-associated homeostasis, growth, and survival in mitochondrial myopathy.","date":"2024","source":"bioRxiv : the preprint server for 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fitness","date":"2025-09-22","source":"bioRxiv","url":"https://doi.org/10.1101/2025.09.22.677734","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":13459,"output_tokens":3078,"usd":0.043273,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10595,"output_tokens":3734,"usd":0.073163,"stage2_stop_reason":"end_turn"},"total_usd":0.116436,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"DELE1 is associated with the inner mitochondrial membrane under steady-state conditions; mitochondrial stress (e.g., membrane depolarization) activates the OMA1 protease, which cleaves DELE1; the resulting short form accumulates in the cytosol where it directly interacts with and activates the eIF2α kinase HRI, triggering the integrated stress response (ISR) and ATF4 translation.\",\n      \"method\": \"Genome-wide CRISPR interference screen, co-immunoprecipitation, subcellular fractionation, in vitro kinase assays, loss-of-function (siRNA/CRISPRi) with defined eIF2α phosphorylation and ATF4 induction readouts\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — two independent labs simultaneously published reciprocal findings using orthogonal genome-wide screens, Co-IP, fractionation, and functional rescue; findings replicated across both studies\",\n      \"pmids\": [\"32132707\", \"32132706\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The C-terminal portion of DELE1 is sufficient to bind and activate HRI in the cytosol; stress-induced OMA1-dependent cleavage generates a short DELE1 form that accumulates in the cytosol and engages HRI via its C-terminal region.\",\n      \"method\": \"Domain-mapping experiments, truncation constructs, Co-IP, functional ISR activation assays in haploid cells and mammalian cells\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — independently replicated in two concurrent studies with multiple orthogonal methods including Co-IP and functional readouts\",\n      \"pmids\": [\"32132706\", \"32132707\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"DELE1 is continuously imported across both mitochondrial membranes into the matrix, surveying diverse perturbations along the import route. Proteolytic removal of N-terminal sorting signals licenses DELE1 molecules in transit for mitochondrial release and stress signaling. Import defects at the mitochondrial surface allow unprocessed DELE1 precursors to bind and activate HRI directly, without the need for OMA1-mediated cleavage. Matrix proteases PITRM1 and MPP also regulate DELE1 activation by controlling presequence processing.\",\n      \"method\": \"Genome-wide genetic screens, subcellular fractionation, import assays, mutational analysis of sorting signals, loss-of-function knockouts of PITRM1/MPP\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide genetics plus multiple orthogonal biochemical approaches in a single focused study with mechanistic validation\",\n      \"pmids\": [\"35388015\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"The cryo-EM structure of the C-terminal cleavage product of human DELE1 reveals it assembles into a high-order octameric complex with D4 symmetry via two sets of hydrophobic inter-subunit interactions. Mutagenesis of key oligomerization residues disrupts octamer formation in vitro and in cells, and assembly-impaired mutants are compromised in their ability to activate HRI-dependent ISR signaling.\",\n      \"method\": \"Cryo-electron microscopy structure determination, site-directed mutagenesis, in vitro reconstitution of oligomer assembly, cell-based ISR activation assays\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — cryo-EM structure combined with mutagenesis and functional validation in vitro and in cells in a single rigorous study\",\n      \"pmids\": [\"37550454\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Under iron-deficient conditions, DELE1 mitochondrial import is arrested, stabilizing DELE1 on the mitochondrial surface to activate HRI-mediated ISR. Under steady-state conditions, DELE1 is degraded by the mitochondrial matrix-resident protease LONP1 shortly after import, limiting basal signaling. Iron chelation blocks LONP1-dependent degradation by preventing complete import.\",\n      \"method\": \"Iron chelation experiments, LONP1 knockout/knockdown, DELE1 import and stability assays, flow cytometry-based cell death assays in erythroid cell models\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods including genetic ablation of LONP1, import assays, and functional ISR readouts in a single focused study\",\n      \"pmids\": [\"37327776\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"DELE1 (originally called DELE) was identified as a direct binding partner of DAP3 (death-associated protein 3). Stable overexpression of DELE1 sensitizes cells to TNF-α- and TRAIL-induced apoptosis, and knockdown of DELE1 rescues cells from apoptosis by these stimuli and inhibits caspase-3, -8, and -9 activation.\",\n      \"method\": \"Yeast two-hybrid screening, co-immunoprecipitation in mammalian cells, stable overexpression, siRNA knockdown with caspase activation readouts\",\n      \"journal\": \"Apoptosis\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — yeast two-hybrid and Co-IP for binding, plus functional knockdown/overexpression with specific caspase readouts; single lab\",\n      \"pmids\": [\"20563667\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Mitochondrial protein import stress (MPIS) is an overarching stress that triggers DELE1 cleavage and HRI activation. Endogenous DELE1 can be cleaved into two forms: DELE1-S (generated under depolarizing stress) and DELE1-VS (generated only under non-depolarizing MPIS). The mitochondrial protease HtrA2 mediates DELE1 cleavage into DELE1-VS; a Parkinson's disease-associated HtrA2 mutant displays reduced DELE1 processing. OMA1 is required for DELE1 cleavage in HeLa cells but is dispensable in HEK293T cells, indicating cell-type-specific protease usage.\",\n      \"method\": \"Endogenous DELE1 detection by western blot, siRNA knockdown of OMA1 and HtrA2 in multiple cell lines, overexpression of PD-associated HtrA2 mutants, DELE1 cleavage assays\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple cell lines and multiple protease knockdowns with defined cleavage product readouts; single lab with orthogonal approaches\",\n      \"pmids\": [\"38555279\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The ISR mediated by DELE1-HRI suppresses PINK1-dependent mitophagy under non-depolarizing mitochondrial stress by positively regulating mitochondrial protein import efficiency, independent of ATF4 activation. Without ISR, increased protein synthesis overwhelms the import machinery, reducing efficiency and enabling PINK1 accumulation to trigger mitophagy.\",\n      \"method\": \"DELE1/HRI loss-of-function, PINK1 accumulation assays, protein import efficiency measurements, ATF4-independent pathway analysis\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — mechanistically defined pathway with multiple genetic knockouts but single lab, preprint only\",\n      \"pmids\": [\"\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Prohibitins (PHBs) regulate DELE1 localization at the inner mitochondrial membrane; targeting PHBs (by fluorizoline treatment or knockdown) impairs the mitochondrial protein import pre-sequence pathway and causes accumulation of DELE1 outside mitochondria, activating ISR via DELE1-HRI. OMA1 is dispensable for ISR activation following PHB targeting, distinguishing this from canonical depolarization-induced DELE1 cleavage.\",\n      \"method\": \"Fluorizoline treatment, PHB siRNA knockdown, DELE1 localization by fractionation, OMA1 knockout/knockdown, ISR activation assays in HeLa and HAP1 cells\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple genetic and pharmacological perturbations with defined mechanistic readouts; single lab but orthogonal approaches\",\n      \"pmids\": [\"41291210\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"De novo designed protein binders engage a critical oligomerization interface on DELE1, block DELE1 oligomerization in vitro while preserving DELE1's ability to bind HRI, and suppress ATF4 induction and ISR activation during mitochondrial stress in cells. A crystal structure of a representative binder confirms engagement of the oligomerization interface, validated by mutagenesis.\",\n      \"method\": \"De novo protein design, in vitro binding and oligomerization assays, crystal structure determination, mutagenesis, cell-based ISR activation (ATF4) assays, mitochondrial morphology imaging\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — crystal structure with mutagenesis and functional validation, but preprint and single lab\",\n      \"pmids\": [\"41717097\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In ovarian cancer cells, OMA1 activation leads to DELE1 cleavage and cytoplasmic interaction of cleaved DELE1 with EIF2AK1 (HRI), which cooperates with ER stress sensor EIF2AK3 to amplify the EIF2S1/ATF4 signal and promote apoptosis. PHB2/STOML2 complex regulates OMA1 protease activity upstream of DELE1.\",\n      \"method\": \"OMA1 knockdown, cisplatin treatment in cells and mouse xenograft models, western blot for DELE1 cleavage and EIF2S1/ATF4, Co-IP for DELE1-EIF2AK1 interaction\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro and in vivo models with multiple genetic and pharmacological perturbations; single lab\",\n      \"pmids\": [\"35163244\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DELE1 is a mitochondrial protein that serves as the central relay of the mitochondrial integrated stress response: under steady-state conditions it is continuously imported into the matrix and rapidly degraded by LONP1, but diverse mitochondrial stresses (membrane depolarization, protein import defects, iron deficiency, inner membrane disruption) trigger OMA1-dependent (or, in some contexts, HtrA2-dependent or import-arrest-dependent) proteolytic processing of DELE1, releasing a short cytosolic fragment that oligomerizes into a D4-symmetric octamer via hydrophobic interfaces and binds/activates the eIF2α kinase HRI, which phosphorylates eIF2α to induce ATF4 and the ISR; DELE1 oligomerization is required for full HRI activation, and the pathway also cross-regulates PINK1-dependent mitophagy by maintaining mitochondrial import efficiency.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DELE1 is the central relay of the mitochondrial integrated stress response (ISR), coupling diverse mitochondrial perturbations to cytosolic eIF2\\u03b1 kinase signaling [#0]. Under steady-state conditions DELE1 is continuously imported across both mitochondrial membranes into the matrix, where it is rapidly degraded by the LONP1 protease, limiting basal signaling; processing of its N-terminal sorting signals by matrix proteases (MPP, PITRM1) and its progression through the import route render it a sensor of import integrity [#2, #4]. Upon mitochondrial stress\\u2014membrane depolarization, import defects, iron deficiency, or inner-membrane perturbation\\u2014the inner-membrane protease OMA1 cleaves DELE1, generating a short C-terminal fragment that accumulates in the cytosol, binds the eIF2\\u03b1 kinase HRI (EIF2AK1) through its C-terminal region, and activates it to phosphorylate eIF2\\u03b1 and induce ATF4 [#0, #1]. The released C-terminal fragment self-assembles into a D4-symmetric octamer via two hydrophobic inter-subunit interfaces, and this oligomerization is required for full HRI activation [#3]. Protease usage is stress- and cell-type-specific: HtrA2 generates an alternative cleavage product under non-depolarizing import stress, and OMA1 is dispensable in certain contexts such as prohibitin-targeted import disruption [#6, #8]; iron deficiency and surface import arrest can stabilize and activate DELE1 independently of OMA1 cleavage [#2, #4]. Beyond inducing ATF4, DELE1\\u2013HRI signaling restrains PINK1-dependent mitophagy by preserving mitochondrial import efficiency [#7]. DELE1 was first identified as a DAP3-binding protein that sensitizes cells to TNF\\u03b1/TRAIL-induced, caspase-dependent apoptosis [#5].\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"Before its mitochondrial role was known, DELE1 was placed in apoptotic signaling, establishing an early functional link to programmed cell death.\",\n      \"evidence\": \"Yeast two-hybrid, Co-IP, and overexpression/knockdown with caspase activation readouts in mammalian cells\",\n      \"pmids\": [\"20563667\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not connect DELE1 to mitochondrial stress sensing or the ISR\", \"Mechanism linking DAP3 binding to caspase activation not resolved\", \"Single lab, no orthogonal validation of the DAP3 interaction\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Established DELE1 as the missing relay between mitochondrial stress and the cytosolic ISR, answering how mitochondrial damage triggers eIF2\\u03b1 phosphorylation.\",\n      \"evidence\": \"Genome-wide CRISPRi screens, Co-IP, fractionation, and in vitro kinase/ISR assays, replicated by two concurrent studies\",\n      \"pmids\": [\"32132707\", \"32132706\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of HRI activation not defined\", \"Full set of activating stresses and proteases not yet mapped\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Mapped the activating determinant to the C-terminal cleavage product, showing the short DELE1 form is the functional HRI-engaging species.\",\n      \"evidence\": \"Truncation/domain-mapping constructs, Co-IP, and functional ISR activation assays in haploid and mammalian cells\",\n      \"pmids\": [\"32132706\", \"32132707\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry of the DELE1\\u2013HRI interaction unknown at this stage\", \"Whether the fragment acts alone or as a complex not yet addressed\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Reframed DELE1 as a surveyor of the mitochondrial import route, explaining how import defects activate signaling without requiring OMA1 cleavage.\",\n      \"evidence\": \"Genome-wide genetic screens, import and fractionation assays, sorting-signal mutagenesis, and PITRM1/MPP knockouts\",\n      \"pmids\": [\"35388015\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How unprocessed precursors engage HRI mechanistically not detailed\", \"Relative contributions of OMA1 vs import-arrest routes in vivo unclear\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Extended the OMA1\\u2013DELE1\\u2013HRI axis to disease, showing it cooperates with ER stress signaling to drive apoptosis in cancer cells.\",\n      \"evidence\": \"OMA1 knockdown, cisplatin treatment in cells and xenografts, Co-IP for DELE1\\u2013EIF2AK1, and EIF2S1/ATF4 western blots\",\n      \"pmids\": [\"35163244\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"PHB2/STOML2 regulation of OMA1 upstream of DELE1 not mechanistically dissected\", \"Single lab; generality across tumor types untested\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Solved the structural mechanism of activation, revealing that the cleaved fragment must oligomerize into a D4-symmetric octamer to fully activate HRI.\",\n      \"evidence\": \"Cryo-EM structure, oligomerization-interface mutagenesis, in vitro reconstitution, and cell-based ISR assays\",\n      \"pmids\": [\"37550454\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structure of the DELE1\\u2013HRI activated complex not determined\", \"How oligomerization converts binding into kinase activation unresolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined LONP1-dependent degradation as the basal brake and import arrest as an OMA1-independent activation mode under iron deficiency.\",\n      \"evidence\": \"Iron chelation, LONP1 knockout/knockdown, import/stability assays, and flow-based cell death assays in erythroid models\",\n      \"pmids\": [\"37327776\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How iron status is sensed by the import machinery not defined\", \"Physiological role in erythropoiesis in vivo not established\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Distinguished stress-specific cleavage products and proteases, identifying HtrA2 as a non-depolarizing-stress protease with Parkinson's-disease relevance.\",\n      \"evidence\": \"Endogenous DELE1 western blots, OMA1/HtrA2 siRNA across cell lines, and PD-associated HtrA2 mutant overexpression\",\n      \"pmids\": [\"38555279\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequences of DELE1-S vs DELE1-VS not fully resolved\", \"Basis for cell-type-specific OMA1 dependence unexplained\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Uncovered an ATF4-independent output of DELE1\\u2013HRI signaling that suppresses PINK1-dependent mitophagy by maintaining import efficiency.\",\n      \"evidence\": \"DELE1/HRI loss-of-function, PINK1 accumulation and import efficiency assays (preprint)\",\n      \"pmids\": [\"\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Preprint, single lab, not peer-reviewed\", \"Molecular link between eIF2\\u03b1 phosphorylation and import efficiency not defined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Implicated prohibitins in controlling DELE1 inner-membrane localization, defining another OMA1-independent route to ISR activation.\",\n      \"evidence\": \"Fluorizoline treatment, PHB knockdown, fractionation, and OMA1 knockout/ISR assays in HeLa and HAP1 cells\",\n      \"pmids\": [\"41291210\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How PHBs physically retain DELE1 at the inner membrane not resolved\", \"Protease, if any, generating the active species after PHB loss unidentified\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Demonstrated the oligomerization interface is a druggable node by designing binders that block octamer assembly and suppress ISR while sparing HRI binding.\",\n      \"evidence\": \"De novo protein design, in vitro binding/oligomerization assays, crystal structure, mutagenesis, and ATF4 ISR assays (preprint)\",\n      \"pmids\": [\"41717097\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Preprint, single lab\", \"In vivo efficacy and selectivity untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the diverse stress inputs, protease choices, and oligomerization state are integrated to set ISR amplitude and to balance survival versus apoptosis or mitophagy remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structure of the activated DELE1 octamer\\u2013HRI complex\", \"Determinants of cell-type-specific protease usage unknown\", \"In vivo physiological and disease roles only partially mapped\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"GO:0140313\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005743\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [2, 4]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953897\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [5, 10]}\n    ],\n    \"complexes\": [\"DELE1 D4-symmetric octamer\"],\n    \"partners\": [\"EIF2AK1\", \"OMA1\", \"LONP1\", \"HTRA2\", \"DAP3\", \"PITRM1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}