{"gene":"DELE1","run_date":"2026-04-28T17:46:02","timeline":{"discoveries":[{"year":2020,"finding":"DELE1 is associated with the inner mitochondrial membrane and, upon mitochondrial stress, is cleaved by the OMA1 protease; the resulting short form accumulates in the cytosol where it directly interacts with and activates the eIF2α kinase HRI, triggering phosphorylation of eIF2α and ATF4 translation as part of the integrated stress response. DELE1 is also required for ATF4 translation downstream of eIF2α phosphorylation.","method":"Genome-wide CRISPR interference screen, subcellular fractionation, co-immunoprecipitation, loss-of-function (knockdown/knockout) with eIF2α phosphorylation and ATF4 induction readouts","journal":"Nature","confidence":"High","confidence_rationale":"Tier 2 — replicated independently by two labs in the same issue with orthogonal genetic and biochemical methods","pmids":["32132707","32132706"],"is_preprint":false},{"year":2020,"finding":"Mitochondrial stress activates OMA1, which cleaves DELE1 into a short form that accumulates in the cytosol and binds HRI via its C-terminal portion to activate HRI-mediated ISR signaling.","method":"Haploid genetic screen, genome engineering, co-immunoprecipitation, truncation mapping, knockdown/knockout with CHOP/eIF2α readouts","journal":"Nature","confidence":"High","confidence_rationale":"Tier 2 — independently replicated, multiple orthogonal methods including genetics and biochemistry","pmids":["32132706","32132707"],"is_preprint":false},{"year":2022,"finding":"DELE1 is continuously sorted across both mitochondrial membranes into the matrix and acts as a sensor of perturbations in mitochondrial protein import and processing. DELE1 molecules in transit become licensed for mitochondrial release and stress signaling through proteolytic removal of N-terminal sorting signals. Import defects at the mitochondrial surface allow uncleaved DELE1 precursors to directly bind and activate HRI without cleavage. DELE1 additionally responds to compromised presequence processing by the matrix proteases PITRM1 and MPP.","method":"Genome-wide genetic screen, subcellular fractionation, import assays, loss-of-function with ISR readouts, domain mapping","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods in one study, mechanistic detail at the level of import intermediates","pmids":["35388015"],"is_preprint":false},{"year":2023,"finding":"Iron deficiency regulates DELE1 through its mitochondrial import: under steady-state conditions DELE1 is degraded by the matrix-resident protease LONP1 after import; upon iron chelation, DELE1 import is arrested, stabilizing DELE1 on the mitochondrial surface to activate HRI-mediated ISR. This defines a mitochondrial iron-responsive pathway.","method":"Iron chelation experiments, LONP1 knockout/knockdown, mitochondrial import assays, co-immunoprecipitation, loss-of-function in erythroid cell model with cell death readout","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods establishing import regulation and downstream signaling","pmids":["37327776"],"is_preprint":false},{"year":2023,"finding":"The C-terminal cleavage product of human DELE1 assembles into a high-order octameric oligomer with D4 symmetry via two sets of hydrophobic inter-subunit interactions. Key oligomerization residues were identified, and assembly-impaired DELE1 mutants are compromised in their ability to activate HRI-dependent ISR signaling in cells.","method":"Cryo-electron microscopy structure determination, in vitro reconstitution, mutagenesis, cell-based ISR activation assays","journal":"Nature structural & molecular biology","confidence":"High","confidence_rationale":"Tier 1 — cryo-EM structure plus mutagenesis and functional validation in cells","pmids":["37550454"],"is_preprint":false},{"year":2010,"finding":"DELE1 (originally named DELE) was identified as a DAP3-binding protein via yeast two-hybrid screening and confirmed to interact with DAP3 in mammalian cells. Stable DELE1 expression sensitizes cells to TNF-α and TRAIL-induced apoptosis; DELE1 knockdown rescues cells from apoptosis and inhibits activation of caspase-3, caspase-8, and caspase-9 induced by TNF-α, anti-Fas, or TRAIL.","method":"Yeast two-hybrid screening, co-immunoprecipitation in mammalian cells, stable overexpression, siRNA knockdown with caspase activation and cell death readouts","journal":"Apoptosis","confidence":"Medium","confidence_rationale":"Tier 3 — single lab, co-IP plus functional phenotype but no in vitro reconstitution or structural validation","pmids":["20563667"],"is_preprint":false},{"year":2024,"finding":"Mitochondrial protein import stress (MPIS) is identified as the overarching stress detected by DELE1. Endogenous DELE1 can be cleaved into two forms: DELE1-S (upon depolarizing stress, OMA1-dependent in HeLa) and DELE1-VS (upon non-depolarizing MPIS, generated during halted translocation). The mitochondrial protease HtrA2 mediates DELE1 cleavage into DELE1-VS; a Parkinson's disease-associated HtrA2 mutant shows reduced DELE1 processing ability. DELE1-S cleavage appears to occur in the cytosol.","method":"Endogenous DELE1 detection, protease knockout/knockdown, HtrA2 mutant analysis, subcellular fractionation, loss-of-function ISR assays","journal":"Communications biology","confidence":"Medium","confidence_rationale":"Tier 2 — multiple proteases tested with loss-of-function, but some cell-line specificity and limited reconstitution","pmids":["38555279"],"is_preprint":false},{"year":2024,"finding":"In mouse models of mitochondrial myopathy, OMA1 and DELE1 sense disruption of the inner mitochondrial membrane and activate the mitochondrial ISR to upregulate pathways for aminoacyl-tRNA biosynthesis and protein synthesis building blocks. Absence of DELE1 (mt-ISR) causes dysregulated protein synthesis, protein misfolding in muscle, and failure of growth and survival in early-onset mitochondrial myopathy mice.","method":"Diverse mouse models (Tfam KO, CHCHD10 G58R and S59L knockin), Dele1 knockout, proteomics, gene expression analysis, growth/survival phenotyping","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal mouse models with defined molecular and organismal phenotypes","pmids":["39379554"],"is_preprint":false},{"year":2025,"finding":"Prohibitins (PHB1/2) regulate the localization and import of DELE1 at the inner mitochondrial membrane; targeting PHBs (by fluorizoline or knockdown) impairs mitochondrial protein import pre-sequence pathway and causes DELE1-dependent ISR activation and apoptosis, with OMA1 dispensable for ISR activation in this context. PHBs interact with DNAJC19 to preserve the mitochondrial protein import pathway.","method":"Fluorizoline treatment, PHB knockdown, DELE1 and OMA1 loss-of-function, localization assays, ISR/apoptosis readouts in HeLa and HAP1 cells","journal":"Cell death and differentiation","confidence":"Medium","confidence_rationale":"Tier 3 — single lab, loss-of-function with mechanistic follow-up but limited biochemical reconstitution","pmids":["41291210"],"is_preprint":false},{"year":2026,"finding":"De novo designed protein binders that engage a critical interface required for DELE1 oligomerization block DELE1 octamer assembly in vitro, suppress ATF4 induction during mitochondrial stress in cells, and impair recovery of mitochondrial morphology, while preserving DELE1's ability to bind HRI. Crystal structure analysis and targeted mutagenesis confirm the binding interface.","method":"De novo protein design, in vitro reconstitution of DELE1 oligomerization, crystal structure determination, targeted mutagenesis, cell-based ATF4/ISR assays","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 1 methods (crystal structure, in vitro reconstitution, mutagenesis) but preprint, single study","pmids":["41717097"],"is_preprint":true},{"year":2024,"finding":"The DELE1-HRI axis of the ISR 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 mitochondrial import machinery, causing PINK1 accumulation and triggering mitophagy.","method":"DELE1/HRI loss-of-function, PINK1 accumulation assays, mitophagy readouts, protein synthesis manipulation under depolarizing and non-depolarizing stress","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 — preprint, single lab, phenotypic data with mechanistic inference but limited biochemical reconstitution","pmids":["38529505"],"is_preprint":true}],"current_model":"DELE1 is a mitochondrial protein that acts as a stress sensor by undergoing regulated import across both mitochondrial membranes; upon diverse mitochondrial stresses, DELE1 is cleaved (primarily by OMA1, and also by HtrA2) or arrested at the mitochondrial surface, allowing its short form or precursor to accumulate in the cytosol where it oligomerizes into an octamer and directly activates the eIF2α kinase HRI, thereby initiating the integrated stress response (eIF2α phosphorylation → ATF4 translation) to maintain cellular and organismal proteostasis."},"narrative":{"teleology":[{"year":2010,"claim":"The initial molecular identity of DELE1 was established as a mitochondrial DAP3-interacting protein that sensitizes cells to death-receptor-induced apoptosis, placing it at the intersection of mitochondria and cell death signaling.","evidence":"Yeast two-hybrid screen for DAP3 partners, co-immunoprecipitation, stable overexpression and siRNA knockdown with caspase activation readouts in mammalian cells","pmids":["20563667"],"confidence":"Medium","gaps":["DAP3 interaction was from a single lab without reciprocal validation or in vitro reconstitution","No connection to stress response signaling was known","Mechanism by which DELE1 promotes caspase activation was undefined"]},{"year":2020,"claim":"Two independent genome-wide screens converged on the OMA1–DELE1–HRI pathway as the mechanism by which mitochondrial stress activates the integrated stress response: OMA1 cleaves inner-membrane-associated DELE1, and the resulting cytosolic short form directly binds and activates HRI to phosphorylate eIF2α and induce ATF4 translation.","evidence":"CRISPRi screen and haploid genetic screen, subcellular fractionation, co-immunoprecipitation, truncation mapping, DELE1/HRI knockout with eIF2α phosphorylation and ATF4 readouts","pmids":["32132707","32132706"],"confidence":"High","gaps":["Structural basis of DELE1–HRI interaction was unknown","How DELE1 senses stresses other than membrane depolarization was unclear","Mechanism by which DELE1 is released from mitochondria was not resolved"]},{"year":2022,"claim":"DELE1 was shown to act as a sensor of mitochondrial protein import fidelity: it is continuously sorted across both membranes into the matrix, and perturbations at any step of import — including surface translocation arrest and compromised presequence processing by PITRM1/MPP — license DELE1 for cytosolic release and HRI activation, even without OMA1-mediated cleavage.","evidence":"Genome-wide genetic screen, mitochondrial import assays, subcellular fractionation, domain mapping, loss-of-function with ISR readouts","pmids":["35388015"],"confidence":"High","gaps":["Relative contribution of different import-arrest intermediates to ISR magnitude was unquantified","Whether full-length DELE1 precursor and cleaved DELE1 activate HRI identically was unresolved","Regulatory role of matrix degradation was not yet characterized"]},{"year":2023,"claim":"The steady-state turnover of DELE1 was found to depend on LONP1-mediated degradation after matrix import, and iron deficiency arrests DELE1 import to stabilize it on the mitochondrial surface for HRI activation, establishing a mitochondrial iron-responsive ISR pathway.","evidence":"Iron chelation experiments, LONP1 knockout/knockdown, mitochondrial import assays, co-immunoprecipitation, erythroid cell model with cell death readout","pmids":["37327776"],"confidence":"High","gaps":["Molecular basis for how iron deficiency impairs DELE1 import was not identified","In vivo relevance to iron deficiency anemia or erythropoiesis was not tested"]},{"year":2023,"claim":"Cryo-EM structure determination revealed that cleaved DELE1 assembles into a D4-symmetric octamer via two hydrophobic interfaces, and mutagenesis of key oligomerization residues demonstrated that octamerization is functionally required for efficient HRI activation in cells.","evidence":"Cryo-EM at near-atomic resolution, in vitro reconstitution, structure-guided mutagenesis, cell-based ISR activation assays","pmids":["37550454"],"confidence":"High","gaps":["Structure of the DELE1 octamer in complex with HRI was not determined","Whether the octamer is the sole signaling-competent species in vivo was unclear","Stoichiometry of the DELE1–HRI signaling complex was unknown"]},{"year":2024,"claim":"The protease landscape was expanded: HtrA2 was identified as an alternative DELE1 protease generating a very-short form (DELE1-VS) under non-depolarizing import stress, a Parkinson's disease-associated HtrA2 mutant showed reduced DELE1 processing, and the concept of mitochondrial protein import stress (MPIS) was proposed as the unifying upstream signal.","evidence":"Endogenous DELE1 detection, protease knockout/knockdown panels, HtrA2 mutant analysis, subcellular fractionation, ISR assays","pmids":["38555279"],"confidence":"Medium","gaps":["HtrA2 cleavage site on DELE1 was not mapped precisely","Functional distinction between DELE1-S and DELE1-VS in activating HRI was not fully resolved","In vivo relevance of HtrA2-mediated cleavage was not demonstrated"]},{"year":2024,"claim":"In vivo loss of DELE1 in multiple mouse models of mitochondrial myopathy demonstrated that DELE1-mediated ISR is essential for organismal proteostasis: without it, dysregulated protein synthesis causes protein misfolding in muscle and compromises growth and survival.","evidence":"Dele1 knockout crossed with Tfam KO and CHCHD10 knockin mouse models, proteomics, gene expression analysis, growth/survival phenotyping","pmids":["39379554"],"confidence":"High","gaps":["Whether DELE1 loss causes similar phenotypes in non-muscle tissues was not tested","Therapeutic potential of enhancing DELE1-ISR axis in mitochondrial disease was not explored","Contribution of ATF4-independent DELE1 functions in vivo was not assessed"]},{"year":2025,"claim":"Prohibitins (PHB1/2) were identified as regulators of DELE1 localization and import at the inner membrane; disruption of prohibitins activates DELE1-dependent ISR independently of OMA1, linking the mitochondrial protein import pre-sequence pathway to ISR through the PHB–DNAJC19 axis.","evidence":"Fluorizoline treatment and PHB knockdown, DELE1 and OMA1 loss-of-function, localization assays, ISR/apoptosis readouts in HeLa and HAP1 cells","pmids":["41291210"],"confidence":"Medium","gaps":["Direct physical interaction between PHBs and DELE1 was not shown","How DNAJC19 mechanistically connects to DELE1 import was not reconstituted","Limited to two cell lines without in vivo validation"]},{"year":null,"claim":"The structure of the DELE1–HRI signaling complex and the precise mechanism by which DELE1 octamers activate HRI kinase remain unresolved, as does the potential ATF4-independent function of DELE1–HRI signaling in regulating mitochondrial protein import and mitophagy.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structure of the DELE1–HRI complex is available","Stoichiometry and dynamics of DELE1–HRI interaction in vivo are unknown","ATF4-independent roles of DELE1–HRI in import regulation and mitophagy suppression lack in vivo confirmation"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,1,4]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,1,2]}],"localization":[{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[0,1,2,3]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,1,4]}],"pathway":[{"term_id":"R-HSA-8953897","term_label":"Cellular responses to stimuli","supporting_discovery_ids":[0,1,2,3,7]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[2,4,7]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[5,8]}],"complexes":["DELE1 octamer"],"partners":["HRI","OMA1","LONP1","HTRA2","DAP3","PHB","PHB2"],"other_free_text":[]},"mechanistic_narrative":"DELE1 is a mitochondrial stress sensor that transduces diverse perturbations of mitochondrial homeostasis into activation of the cytosolic integrated stress response (ISR). Under basal conditions, DELE1 is continuously imported across both mitochondrial membranes and degraded by the matrix protease LONP1; upon mitochondrial stress — including membrane depolarization, impaired protein import, compromised presequence processing, or iron deficiency — DELE1 is either cleaved by OMA1 or HtrA2 or arrested at the mitochondrial surface, causing its accumulation in the cytosol where its C-terminal portion assembles into a D4-symmetric octamer that directly binds and activates the eIF2α kinase HRI, triggering eIF2α phosphorylation and ATF4 translation [PMID:32132707, PMID:32132706, PMID:35388015, PMID:37327776, PMID:37550454, PMID:38555279]. Octamerization through hydrophobic inter-subunit contacts is required for efficient HRI activation, as assembly-impaired mutants fail to induce ISR signaling [PMID:37550454]. In mouse models of mitochondrial myopathy, DELE1-mediated ISR activation maintains proteostasis by upregulating aminoacyl-tRNA biosynthesis; loss of DELE1 causes protein misfolding and compromised growth and survival [PMID:39379554]."},"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":504,"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":386,"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":75,"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":60,"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":36,"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":20,"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":"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":15,"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":15,"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":9,"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":"41291210","id":"PMC_41291210","title":"Targeting prohibitins activates the ISR through DELE1-HRI by impairing protein import into the mitochondrial matrix.","date":"2025","source":"Cell death and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/41291210","citation_count":1,"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 biology","url":"https://pubmed.ncbi.nlm.nih.gov/38529505","citation_count":1,"is_preprint":false},{"pmid":"41422903","id":"PMC_41422903","title":"Trifloxystrobin induces oxidative stress-dependent activation of the OMA1-DELE1-HRI integrated stress response leading to apoptosis in human neuroblastoma cells.","date":"2025","source":"Environmental pollution (Barking, Essex : 1987)","url":"https://pubmed.ncbi.nlm.nih.gov/41422903","citation_count":1,"is_preprint":false},{"pmid":"41717097","id":"PMC_41717097","title":"De novo design of protein binders that target DELE1 to inhibit the mitochondrial stress response.","date":"2026","source":"bioRxiv : the preprint server for 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Cells","date":"2025-06-26","source":"bioRxiv","url":"https://doi.org/10.1101/2025.06.23.660251","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.10.16.617214","title":"The Integrated Stress Response Suppresses PINK1-dependent Mitophagy by Preserving Mitochondrial Import Efficiency","date":"2024-10-17","source":"bioRxiv","url":"https://doi.org/10.1101/2024.10.16.617214","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.06.02.597064","title":"Skeletal Muscle Specific PolG Dysfunction Activates the Integrated Stress Response and Promotes a Cachexia like Phenotype","date":"2024-06-03","source":"bioRxiv","url":"https://doi.org/10.1101/2024.06.02.597064","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.09.22.677734","title":"The mitochondrial disulphide relay substrate FAM136A safeguards IMS proteostasis and cellular 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":12188,"output_tokens":2862,"usd":0.039747},"stage2":{"model":"claude-opus-4-6","input_tokens":6234,"output_tokens":2798,"usd":0.15168},"total_usd":0.191427,"stage1_batch_id":"msgbatch_0118RScg3WGaGkaZRtWZbtce","stage2_batch_id":"msgbatch_01Cpfzvtbj42aqp5oYZ5Te2s","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 and, upon mitochondrial stress, is cleaved by the OMA1 protease; the resulting short form accumulates in the cytosol where it directly interacts with and activates the eIF2α kinase HRI, triggering phosphorylation of eIF2α and ATF4 translation as part of the integrated stress response. DELE1 is also required for ATF4 translation downstream of eIF2α phosphorylation.\",\n      \"method\": \"Genome-wide CRISPR interference screen, subcellular fractionation, co-immunoprecipitation, loss-of-function (knockdown/knockout) with eIF2α phosphorylation and ATF4 induction readouts\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — replicated independently by two labs in the same issue with orthogonal genetic and biochemical methods\",\n      \"pmids\": [\"32132707\", \"32132706\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Mitochondrial stress activates OMA1, which cleaves DELE1 into a short form that accumulates in the cytosol and binds HRI via its C-terminal portion to activate HRI-mediated ISR signaling.\",\n      \"method\": \"Haploid genetic screen, genome engineering, co-immunoprecipitation, truncation mapping, knockdown/knockout with CHOP/eIF2α readouts\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — independently replicated, multiple orthogonal methods including genetics and biochemistry\",\n      \"pmids\": [\"32132706\", \"32132707\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"DELE1 is continuously sorted across both mitochondrial membranes into the matrix and acts as a sensor of perturbations in mitochondrial protein import and processing. DELE1 molecules in transit become licensed for mitochondrial release and stress signaling through proteolytic removal of N-terminal sorting signals. Import defects at the mitochondrial surface allow uncleaved DELE1 precursors to directly bind and activate HRI without cleavage. DELE1 additionally responds to compromised presequence processing by the matrix proteases PITRM1 and MPP.\",\n      \"method\": \"Genome-wide genetic screen, subcellular fractionation, import assays, loss-of-function with ISR readouts, domain mapping\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods in one study, mechanistic detail at the level of import intermediates\",\n      \"pmids\": [\"35388015\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Iron deficiency regulates DELE1 through its mitochondrial import: under steady-state conditions DELE1 is degraded by the matrix-resident protease LONP1 after import; upon iron chelation, DELE1 import is arrested, stabilizing DELE1 on the mitochondrial surface to activate HRI-mediated ISR. This defines a mitochondrial iron-responsive pathway.\",\n      \"method\": \"Iron chelation experiments, LONP1 knockout/knockdown, mitochondrial import assays, co-immunoprecipitation, loss-of-function in erythroid cell model with cell death readout\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods establishing import regulation and downstream signaling\",\n      \"pmids\": [\"37327776\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"The C-terminal cleavage product of human DELE1 assembles into a high-order octameric oligomer with D4 symmetry via two sets of hydrophobic inter-subunit interactions. Key oligomerization residues were identified, and assembly-impaired DELE1 mutants are compromised in their ability to activate HRI-dependent ISR signaling in cells.\",\n      \"method\": \"Cryo-electron microscopy structure determination, in vitro reconstitution, mutagenesis, cell-based ISR activation assays\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — cryo-EM structure plus mutagenesis and functional validation in cells\",\n      \"pmids\": [\"37550454\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"DELE1 (originally named DELE) was identified as a DAP3-binding protein via yeast two-hybrid screening and confirmed to interact with DAP3 in mammalian cells. Stable DELE1 expression sensitizes cells to TNF-α and TRAIL-induced apoptosis; DELE1 knockdown rescues cells from apoptosis and inhibits activation of caspase-3, caspase-8, and caspase-9 induced by TNF-α, anti-Fas, or TRAIL.\",\n      \"method\": \"Yeast two-hybrid screening, co-immunoprecipitation in mammalian cells, stable overexpression, siRNA knockdown with caspase activation and cell death readouts\",\n      \"journal\": \"Apoptosis\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — single lab, co-IP plus functional phenotype but no in vitro reconstitution or structural validation\",\n      \"pmids\": [\"20563667\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Mitochondrial protein import stress (MPIS) is identified as the overarching stress detected by DELE1. Endogenous DELE1 can be cleaved into two forms: DELE1-S (upon depolarizing stress, OMA1-dependent in HeLa) and DELE1-VS (upon non-depolarizing MPIS, generated during halted translocation). The mitochondrial protease HtrA2 mediates DELE1 cleavage into DELE1-VS; a Parkinson's disease-associated HtrA2 mutant shows reduced DELE1 processing ability. DELE1-S cleavage appears to occur in the cytosol.\",\n      \"method\": \"Endogenous DELE1 detection, protease knockout/knockdown, HtrA2 mutant analysis, subcellular fractionation, loss-of-function ISR assays\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple proteases tested with loss-of-function, but some cell-line specificity and limited reconstitution\",\n      \"pmids\": [\"38555279\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"In mouse models of mitochondrial myopathy, OMA1 and DELE1 sense disruption of the inner mitochondrial membrane and activate the mitochondrial ISR to upregulate pathways for aminoacyl-tRNA biosynthesis and protein synthesis building blocks. Absence of DELE1 (mt-ISR) causes dysregulated protein synthesis, protein misfolding in muscle, and failure of growth and survival in early-onset mitochondrial myopathy mice.\",\n      \"method\": \"Diverse mouse models (Tfam KO, CHCHD10 G58R and S59L knockin), Dele1 knockout, proteomics, gene expression analysis, growth/survival phenotyping\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal mouse models with defined molecular and organismal phenotypes\",\n      \"pmids\": [\"39379554\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Prohibitins (PHB1/2) regulate the localization and import of DELE1 at the inner mitochondrial membrane; targeting PHBs (by fluorizoline or knockdown) impairs mitochondrial protein import pre-sequence pathway and causes DELE1-dependent ISR activation and apoptosis, with OMA1 dispensable for ISR activation in this context. PHBs interact with DNAJC19 to preserve the mitochondrial protein import pathway.\",\n      \"method\": \"Fluorizoline treatment, PHB knockdown, DELE1 and OMA1 loss-of-function, localization assays, ISR/apoptosis readouts in HeLa and HAP1 cells\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — single lab, loss-of-function with mechanistic follow-up but limited biochemical reconstitution\",\n      \"pmids\": [\"41291210\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"De novo designed protein binders that engage a critical interface required for DELE1 oligomerization block DELE1 octamer assembly in vitro, suppress ATF4 induction during mitochondrial stress in cells, and impair recovery of mitochondrial morphology, while preserving DELE1's ability to bind HRI. Crystal structure analysis and targeted mutagenesis confirm the binding interface.\",\n      \"method\": \"De novo protein design, in vitro reconstitution of DELE1 oligomerization, crystal structure determination, targeted mutagenesis, cell-based ATF4/ISR assays\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 methods (crystal structure, in vitro reconstitution, mutagenesis) but preprint, single study\",\n      \"pmids\": [\"41717097\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The DELE1-HRI axis of the ISR 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 mitochondrial import machinery, causing PINK1 accumulation and triggering mitophagy.\",\n      \"method\": \"DELE1/HRI loss-of-function, PINK1 accumulation assays, mitophagy readouts, protein synthesis manipulation under depolarizing and non-depolarizing stress\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — preprint, single lab, phenotypic data with mechanistic inference but limited biochemical reconstitution\",\n      \"pmids\": [\"38529505\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"DELE1 is a mitochondrial protein that acts as a stress sensor by undergoing regulated import across both mitochondrial membranes; upon diverse mitochondrial stresses, DELE1 is cleaved (primarily by OMA1, and also by HtrA2) or arrested at the mitochondrial surface, allowing its short form or precursor to accumulate in the cytosol where it oligomerizes into an octamer and directly activates the eIF2α kinase HRI, thereby initiating the integrated stress response (eIF2α phosphorylation → ATF4 translation) to maintain cellular and organismal proteostasis.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"DELE1 is a mitochondrial stress sensor that transduces diverse perturbations of mitochondrial homeostasis into activation of the cytosolic integrated stress response (ISR). Under basal conditions, DELE1 is continuously imported across both mitochondrial membranes and degraded by the matrix protease LONP1; upon mitochondrial stress — including membrane depolarization, impaired protein import, compromised presequence processing, or iron deficiency — DELE1 is either cleaved by OMA1 or HtrA2 or arrested at the mitochondrial surface, causing its accumulation in the cytosol where its C-terminal portion assembles into a D4-symmetric octamer that directly binds and activates the eIF2α kinase HRI, triggering eIF2α phosphorylation and ATF4 translation [PMID:32132707, PMID:32132706, PMID:35388015, PMID:37327776, PMID:37550454, PMID:38555279]. Octamerization through hydrophobic inter-subunit contacts is required for efficient HRI activation, as assembly-impaired mutants fail to induce ISR signaling [PMID:37550454]. In mouse models of mitochondrial myopathy, DELE1-mediated ISR activation maintains proteostasis by upregulating aminoacyl-tRNA biosynthesis; loss of DELE1 causes protein misfolding and compromised growth and survival [PMID:39379554].\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"The initial molecular identity of DELE1 was established as a mitochondrial DAP3-interacting protein that sensitizes cells to death-receptor-induced apoptosis, placing it at the intersection of mitochondria and cell death signaling.\",\n      \"evidence\": \"Yeast two-hybrid screen for DAP3 partners, co-immunoprecipitation, stable overexpression and siRNA knockdown with caspase activation readouts in mammalian cells\",\n      \"pmids\": [\"20563667\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"DAP3 interaction was from a single lab without reciprocal validation or in vitro reconstitution\",\n        \"No connection to stress response signaling was known\",\n        \"Mechanism by which DELE1 promotes caspase activation was undefined\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Two independent genome-wide screens converged on the OMA1–DELE1–HRI pathway as the mechanism by which mitochondrial stress activates the integrated stress response: OMA1 cleaves inner-membrane-associated DELE1, and the resulting cytosolic short form directly binds and activates HRI to phosphorylate eIF2α and induce ATF4 translation.\",\n      \"evidence\": \"CRISPRi screen and haploid genetic screen, subcellular fractionation, co-immunoprecipitation, truncation mapping, DELE1/HRI knockout with eIF2α phosphorylation and ATF4 readouts\",\n      \"pmids\": [\"32132707\", \"32132706\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of DELE1–HRI interaction was unknown\",\n        \"How DELE1 senses stresses other than membrane depolarization was unclear\",\n        \"Mechanism by which DELE1 is released from mitochondria was not resolved\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"DELE1 was shown to act as a sensor of mitochondrial protein import fidelity: it is continuously sorted across both membranes into the matrix, and perturbations at any step of import — including surface translocation arrest and compromised presequence processing by PITRM1/MPP — license DELE1 for cytosolic release and HRI activation, even without OMA1-mediated cleavage.\",\n      \"evidence\": \"Genome-wide genetic screen, mitochondrial import assays, subcellular fractionation, domain mapping, loss-of-function with ISR readouts\",\n      \"pmids\": [\"35388015\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Relative contribution of different import-arrest intermediates to ISR magnitude was unquantified\",\n        \"Whether full-length DELE1 precursor and cleaved DELE1 activate HRI identically was unresolved\",\n        \"Regulatory role of matrix degradation was not yet characterized\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The steady-state turnover of DELE1 was found to depend on LONP1-mediated degradation after matrix import, and iron deficiency arrests DELE1 import to stabilize it on the mitochondrial surface for HRI activation, establishing a mitochondrial iron-responsive ISR pathway.\",\n      \"evidence\": \"Iron chelation experiments, LONP1 knockout/knockdown, mitochondrial import assays, co-immunoprecipitation, erythroid cell model with cell death readout\",\n      \"pmids\": [\"37327776\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular basis for how iron deficiency impairs DELE1 import was not identified\",\n        \"In vivo relevance to iron deficiency anemia or erythropoiesis was not tested\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Cryo-EM structure determination revealed that cleaved DELE1 assembles into a D4-symmetric octamer via two hydrophobic interfaces, and mutagenesis of key oligomerization residues demonstrated that octamerization is functionally required for efficient HRI activation in cells.\",\n      \"evidence\": \"Cryo-EM at near-atomic resolution, in vitro reconstitution, structure-guided mutagenesis, cell-based ISR activation assays\",\n      \"pmids\": [\"37550454\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structure of the DELE1 octamer in complex with HRI was not determined\",\n        \"Whether the octamer is the sole signaling-competent species in vivo was unclear\",\n        \"Stoichiometry of the DELE1–HRI signaling complex was unknown\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"The protease landscape was expanded: HtrA2 was identified as an alternative DELE1 protease generating a very-short form (DELE1-VS) under non-depolarizing import stress, a Parkinson's disease-associated HtrA2 mutant showed reduced DELE1 processing, and the concept of mitochondrial protein import stress (MPIS) was proposed as the unifying upstream signal.\",\n      \"evidence\": \"Endogenous DELE1 detection, protease knockout/knockdown panels, HtrA2 mutant analysis, subcellular fractionation, ISR assays\",\n      \"pmids\": [\"38555279\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"HtrA2 cleavage site on DELE1 was not mapped precisely\",\n        \"Functional distinction between DELE1-S and DELE1-VS in activating HRI was not fully resolved\",\n        \"In vivo relevance of HtrA2-mediated cleavage was not demonstrated\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"In vivo loss of DELE1 in multiple mouse models of mitochondrial myopathy demonstrated that DELE1-mediated ISR is essential for organismal proteostasis: without it, dysregulated protein synthesis causes protein misfolding in muscle and compromises growth and survival.\",\n      \"evidence\": \"Dele1 knockout crossed with Tfam KO and CHCHD10 knockin mouse models, proteomics, gene expression analysis, growth/survival phenotyping\",\n      \"pmids\": [\"39379554\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether DELE1 loss causes similar phenotypes in non-muscle tissues was not tested\",\n        \"Therapeutic potential of enhancing DELE1-ISR axis in mitochondrial disease was not explored\",\n        \"Contribution of ATF4-independent DELE1 functions in vivo was not assessed\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Prohibitins (PHB1/2) were identified as regulators of DELE1 localization and import at the inner membrane; disruption of prohibitins activates DELE1-dependent ISR independently of OMA1, linking the mitochondrial protein import pre-sequence pathway to ISR through the PHB–DNAJC19 axis.\",\n      \"evidence\": \"Fluorizoline treatment and PHB knockdown, DELE1 and OMA1 loss-of-function, localization assays, ISR/apoptosis readouts in HeLa and HAP1 cells\",\n      \"pmids\": [\"41291210\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct physical interaction between PHBs and DELE1 was not shown\",\n        \"How DNAJC19 mechanistically connects to DELE1 import was not reconstituted\",\n        \"Limited to two cell lines without in vivo validation\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The structure of the DELE1–HRI signaling complex and the precise mechanism by which DELE1 octamers activate HRI kinase remain unresolved, as does the potential ATF4-independent function of DELE1–HRI signaling in regulating mitochondrial protein import and mitophagy.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structure of the DELE1–HRI complex is available\",\n        \"Stoichiometry and dynamics of DELE1–HRI interaction in vivo are unknown\",\n        \"ATF4-independent roles of DELE1–HRI in import regulation and mitophagy suppression lack in vivo confirmation\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0, 1, 2, 3]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 1, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953897\", \"supporting_discovery_ids\": [0, 1, 2, 3, 7]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [2, 4, 7]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [5, 8]}\n    ],\n    \"complexes\": [\n      \"DELE1 octamer\"\n    ],\n    \"partners\": [\n      \"HRI\",\n      \"OMA1\",\n      \"LONP1\",\n      \"HTRA2\",\n      \"DAP3\",\n      \"PHB\",\n      \"PHB2\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}