{"gene":"DNAJC19","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2003,"finding":"Tim14 (DNAJC19 yeast ortholog) is an integral inner mitochondrial membrane protein with a J-domain exposed to the matrix; it is an essential component of the TIM23 import motor, stimulates the ATPase activity of mtHsp70, and interacts with Tim44 and mtHsp70 in an ATP-dependent manner. Mutation of the HPD motif of the J-domain is lethal.","method":"Genetic depletion in yeast, mitochondrial protein import assays, co-immunoprecipitation, HPD motif mutagenesis","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal methods (depletion, import assays, Co-IP, mutagenesis) in a single rigorous study establishing essential function","pmids":["14517234"],"is_preprint":false},{"year":2004,"finding":"Pam18 (DNAJC19 yeast ortholog) forms a complex with Pam16; Pam16 specifically antagonizes/inhibits Pam18-mediated stimulation of mtHsp70 ATPase activity. Pam16 lacking the HPD motif cannot stimulate mtHsp70 but can still inhibit Pam18.","method":"In vitro ATPase stimulation assays, genetic complementation in yeast, biochemical inhibition assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro ATPase assays combined with in vivo genetic complementation and mutagenesis","pmids":["15218029"],"is_preprint":false},{"year":2005,"finding":"DNAJC19 is localized to mitochondria (inner mitochondrial membrane) in cardiac myocytes and shares sequence/organizational similarity with yeast Tim14 and Mdj2. A splice-site mutation (IVS3-1 G→C) causing DCMA syndrome was identified, establishing DNAJC19 as a component of the mitochondrial protein import pathway.","method":"Homozygosity mapping, mutation sequencing, RT-PCR, bioinformatics","journal":"Journal of medical genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic mapping and sequence analysis with prior localization data; mechanism inferred by homology to yeast proteins","pmids":["16055927"],"is_preprint":false},{"year":2005,"finding":"The yeast import motor contains two J-proteins, Tim14 and Mdj2; Mdj2 forms a complex with Tim16, is recruited to TIM23 translocase, and stimulates mtHsp70 ATPase to the same extent as Tim14. Overexpressed Mdj2 fully rescues Tim14-null growth defect.","method":"Yeast genetics (deletion strains), biochemical co-purification, ATPase stimulation assays, overexpression complementation","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal biochemical and genetic methods in a single study","pmids":["16027163"],"is_preprint":false},{"year":2006,"finding":"Crystal structure of the Tim14-Tim16 (Pam18-Pam16) complex shows the conserved domains have virtually identical folds but completely different surfaces. Tim16 tightly regulates the cochaperone activity of Tim14. Mutations destroying the Tim14-Tim16 complex are lethal.","method":"X-ray crystallography, mutagenesis, in vitro ATPase activity assays, yeast viability assays","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure combined with mutagenesis and functional assays in a single rigorous study","pmids":["16977310"],"is_preprint":false},{"year":2007,"finding":"The Pam18:Pam16 heterodimer associates with the TIM23 translocon via three interactions: the N-terminus of Pam16 with the matrix side of the translocon, the IMS domain of Pam18 with Tim17, and direct J-domain:J-like-domain interaction. Pam16 plays the major role in translocon association; disruption of heterodimer stability dramatically reduces Pam18 (but not Pam16) association with the translocon.","method":"Biochemical co-purification, yeast genetic suppressor screen, domain deletion/mutagenesis, co-immunoprecipitation","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal biochemical assays, suppressor screen, domain mapping, multiple orthogonal methods","pmids":["18003975"],"is_preprint":false},{"year":2007,"finding":"The hydrophobic N-terminal segment of Tim16 (yeast Pam16) is crucial for interaction of the Tim14·Tim16 complex with the core TIM23 translocase. Deletion of hydrophobic segments from both Tim16 and Tim14 is lethal; deletion of either alone causes growth defects and decreased matrix-protein import.","method":"Yeast genetics (deletion mutants), mitochondrial import assays, co-immunoprecipitation","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic and biochemical complementation with import assays and Co-IP","pmids":["17452317"],"is_preprint":false},{"year":2007,"finding":"The Pam18/Tim14-Pam16/Tim16 heterodimer is thermally more stable (Tm ~41°C) than either individual subunit (Tm 16.5°C and 29°C respectively), demonstrating stabilization upon complex formation.","method":"CD spectroscopy, chemical crosslinking (DSS), thermal denaturation, in vitro co-overexpression and purification","journal":"Protein science","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro structural characterization by a single lab with clear biophysical methods but no functional readout beyond stability","pmids":["17242434"],"is_preprint":false},{"year":2009,"finding":"The soluble domains of human DNAJC19 (Tim14/Pam18) and human Tim16/Pam16 interact with their yeast counterparts, forming heterodimeric complexes, and these hybrid complexes interact with yeast mtHsp70, demonstrating structural conservation across species.","method":"Recombinant protein purification, in vitro binding assays, cross-species heterodimer formation","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro reconstitution of heterodimer and mtHsp70 interaction, single lab, two orthogonal methods","pmids":["19564938"],"is_preprint":false},{"year":2011,"finding":"The Pam18:Pam16 heterodimer interaction is required for physical tethering of Pam18 to the TIM23 translocon (via Pam16) rather than primarily for inhibiting Pam18's ATPase-stimulatory activity; a previously uncharacterized region of Pam16 is required for forming an active Pam18:Pam16 complex that can stimulate mtHsp70 ATPase activity.","method":"Biochemical ATPase assays, genetic interaction analysis, in vivo yeast complementation, domain mapping","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — biochemical and genetic assays in a single lab; partially revises prior model with multiple methods","pmids":["22031295"],"is_preprint":false},{"year":2014,"finding":"DNAJC19 forms a complex with prohibitin (PHB) complexes in the inner mitochondrial membrane. Loss of DNAJC19 or PHB2 leads to impaired cell growth, defective cristae morphogenesis, and accumulation of cardiolipin species with altered acyl chains. PHB/DNAJC19 membrane domains regulate cardiolipin remodeling by tafazzin.","method":"PHB2 interactome mass spectrometry, Co-immunoprecipitation, cell growth assays, cardiolipin lipidomic analysis, gene knockout/knockdown","journal":"Cell metabolism","confidence":"High","confidence_rationale":"Tier 2 / Strong — interactome MS, reciprocal Co-IP, lipidomics, and cellular phenotypic assays across multiple conditions in a single study","pmids":["24856930"],"is_preprint":false},{"year":2022,"finding":"Disruption of the Pam16-Pam18 heterodimer causes redistribution of Pam18 to respiratory chain supercomplexes where it forms a homodimer; this redistribution decreases protein import into mitochondria but stimulates mtHsp70-dependent assembly of respiratory chain complexes, revealing a dual function of the Pam16-Pam18 module.","method":"Yeast genetics, co-immunoprecipitation, mitochondrial protein import assays, respiratory chain complex assembly assays","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (Co-IP, import assays, assembly assays, genetics) in a single study establishing dual localization and function","pmids":["35385740"],"is_preprint":false},{"year":2023,"finding":"Loss of the DnaJ interaction domain in DNAJC19 (truncation variant) causes mitochondrial fragmentation, abnormal cristae formation, reduced mitochondrial protein expression, increased oxygen consumption rate, altered substrate utilization (decreased fatty acid uptake, increased glucose utilization), elevated ROS, increased mitochondrial membrane potential, and dysregulated Ca2+ kinetics in iPSC-derived cardiomyocytes.","method":"iPSC-derived cardiomyocyte models (patient-derived and CRISPR gene-edited), electron microscopy, Seahorse respirometry, radioactive tracer uptake assays, ROS measurements, Ca2+ imaging, sarcomere shortening analysis","journal":"Molecular metabolism","confidence":"High","confidence_rationale":"Tier 2 / Strong — patient-derived and gene-edited cell models with multiple orthogonal functional assays in a single study","pmids":["38142971"],"is_preprint":false},{"year":2025,"finding":"Pam18 (DNAJC19 yeast ortholog) is specifically targeted for degradation by the Lon/Pim1 mitochondrial matrix protease both in vitro and in vivo; overexpression of Pam18 exacerbates growth defects in Δpim1 cells, establishing Lon/Pim1 as a regulator of Pam18 protein homeostasis.","method":"In vitro degradation assays with purified Lon/Pim1, in vivo yeast genetics (Δpim1 strain), overexpression studies","journal":"The Biochemical journal","confidence":"Medium","confidence_rationale":"Tier 1-2 / Moderate — in vitro and in vivo assays in single lab, two orthogonal approaches","pmids":["41099349"],"is_preprint":false}],"current_model":"DNAJC19 (Tim14/Pam18) is an inner mitochondrial membrane J-protein that, as part of the TIM23 presequence translocase-associated motor, stimulates the ATPase activity of mtHsp70 to drive ATP-dependent protein import into the mitochondrial matrix; it forms an essential heterodimer with the J-like protein Tim16/Pam16—whose crystal structure has been solved—which regulates DNAJC19's cochaperone activity and tethers it to the translocon via Tim17 and Tim44 interactions; additionally, DNAJC19 forms a complex with prohibitins in the inner membrane to regulate tafazzin-mediated cardiolipin remodeling, and loss of its DnaJ domain causes mitochondrial fragmentation, cristae defects, altered cardiolipin acylation, and metabolic dysfunction underlying dilated cardiomyopathy with ataxia (DCMA) syndrome."},"narrative":{"mechanistic_narrative":"DNAJC19 (Tim14/Pam18) is an inner mitochondrial membrane J-protein that functions as the essential J-domain cochaperone of the TIM23 presequence translocase-associated import motor, stimulating the ATPase activity of mtHsp70 to drive ATP-dependent translocation of precursor proteins into the matrix [PMID:14517234]. Its activity is governed by an obligate heterodimer with the J-like protein Tim16/Pam16: structural and biochemical work shows the two share nearly identical folds but distinct surfaces, with Tim16 tightly regulating DNAJC19's cochaperone output, and disruption of the complex being lethal [PMID:15218029, PMID:16977310]. Heterodimer formation also stabilizes both subunits and tethers DNAJC19 to the translocon, where Tim16 makes the major contacts via its N-terminal hydrophobic segment and the matrix face of the channel while the DNAJC19 IMS domain engages Tim17, so that loss of heterodimer integrity strips DNAJC19 from the translocon and impairs matrix import [PMID:18003975, PMID:17452317, PMID:17242434]. Beyond import, DNAJC19 has a second function: it associates with prohibitin (PHB) membrane domains in the inner membrane to organize tafazzin-mediated cardiolipin remodeling, and its loss produces defective cristae morphogenesis and accumulation of cardiolipin species with altered acyl chains [PMID:24856930]. Truncation removing the DnaJ interaction domain causes mitochondrial fragmentation, abnormal cristae, altered substrate utilization, elevated ROS and dysregulated Ca2+ handling in cardiomyocytes [PMID:38142971]. A splice-site mutation in DNAJC19 causes dilated cardiomyopathy with ataxia (DCMA) syndrome [PMID:16055927].","teleology":[{"year":2003,"claim":"Established that the yeast ortholog Tim14 is an essential matrix-facing J-protein of the TIM23 import motor that drives mtHsp70-powered protein import, defining the core molecular activity of this protein family.","evidence":"Genetic depletion, import assays, Co-IP, and HPD-motif mutagenesis in yeast","pmids":["14517234"],"confidence":"High","gaps":["Did not address regulation of J-domain activity by partner subunits","Human ortholog not directly characterized"]},{"year":2004,"claim":"Identified the regulatory partner Pam16 and showed it antagonizes Pam18-mediated mtHsp70 ATPase stimulation, revealing that cochaperone output is held in check by a J-like partner.","evidence":"In vitro ATPase assays, genetic complementation, and HPD-mutant inhibition assays in yeast","pmids":["15218029"],"confidence":"High","gaps":["Structural basis of the Pam16 antagonism not resolved","Whether inhibition operates at the translocon in vivo not yet defined"]},{"year":2005,"claim":"Connected the gene to human disease, localizing DNAJC19 to the cardiac inner mitochondrial membrane and identifying a splice-site mutation causing DCMA syndrome.","evidence":"Homozygosity mapping, mutation sequencing, RT-PCR, and bioinformatics","pmids":["16055927"],"confidence":"Medium","gaps":["Mechanism inferred by homology to yeast Tim14 rather than direct human assays","Did not establish how import defect produces cardiomyopathy"]},{"year":2005,"claim":"Showed the motor harbors a second J-protein, Mdj2, that can functionally substitute for Tim14, refining understanding of J-protein redundancy at the translocon.","evidence":"Yeast deletion strains, co-purification, ATPase assays, and overexpression complementation","pmids":["16027163"],"confidence":"High","gaps":["Physiological role of two J-proteins not delineated","No mammalian counterpart of this redundancy described"]},{"year":2006,"claim":"Provided the structural basis for heterodimer-regulated cochaperone activity by solving the Tim14-Tim16 complex, showing identical folds with divergent surfaces and lethal phenotypes upon complex disruption.","evidence":"X-ray crystallography with mutagenesis, ATPase assays, and yeast viability tests","pmids":["16977310"],"confidence":"High","gaps":["Structure of the full translocon-bound module not resolved","Human complex structure not determined"]},{"year":2007,"claim":"Defined how the heterodimer docks onto the translocon, mapping three interactions and assigning Tim16 the dominant tethering role via its hydrophobic N-terminus, and showed heterodimer formation thermally stabilizes both subunits.","evidence":"Co-purification, suppressor screens, domain mapping, import assays, CD spectroscopy and crosslinking in yeast","pmids":["18003975","17452317","17242434"],"confidence":"High","gaps":["Dynamics of docking during active import not captured","Quantitative contribution of each contact to import flux unresolved"]},{"year":2009,"claim":"Demonstrated cross-species conservation by showing human DNAJC19 and human Tim16 form heterodimers and engage mtHsp70 even when paired with yeast counterparts, extending the yeast model to the human proteins.","evidence":"Recombinant protein purification and in vitro cross-species heterodimer binding assays","pmids":["19564938"],"confidence":"Medium","gaps":["No functional import assay in human mitochondria","Native human translocon context not tested"]},{"year":2011,"claim":"Revised the regulatory model, showing the Pam18:Pam16 interaction primarily serves to physically tether Pam18 to the translocon rather than to inhibit its activity, and identified a Pam16 region required to form an active stimulatory complex.","evidence":"ATPase assays, genetic interaction analysis, and domain mapping in yeast","pmids":["22031295"],"confidence":"Medium","gaps":["Reconciliation with the earlier antagonism model not fully settled","Region of Pam16 not structurally defined"]},{"year":2014,"claim":"Uncovered a second, import-independent function by showing DNAJC19 partners with prohibitin domains to regulate tafazzin-mediated cardiolipin remodeling and cristae morphology, linking it directly to membrane lipid homeostasis.","evidence":"PHB2 interactome MS, reciprocal Co-IP, cardiolipin lipidomics, and knockout/knockdown phenotyping","pmids":["24856930"],"confidence":"High","gaps":["Molecular mechanism by which DNAJC19 controls tafazzin not defined","Relationship between import role and cardiolipin role unresolved"]},{"year":2022,"claim":"Revealed a moonlighting function in which heterodimer disruption redistributes Pam18 to respiratory chain supercomplexes as a homodimer, where it promotes mtHsp70-dependent complex assembly at the cost of import.","evidence":"Yeast genetics, Co-IP, import assays, and respiratory chain assembly assays","pmids":["35385740"],"confidence":"High","gaps":["Whether human DNAJC19 shares this dual localization not tested","Trigger for physiological redistribution unknown"]},{"year":2023,"claim":"Connected the disease truncation to cellular phenotype, showing loss of the DnaJ interaction domain drives mitochondrial fragmentation, cristae defects, metabolic reprogramming, ROS elevation and Ca2+ dysregulation in cardiomyocytes.","evidence":"Patient-derived and CRISPR-edited iPSC-cardiomyocytes with EM, Seahorse respirometry, tracer uptake, ROS and Ca2+ imaging","pmids":["38142971"],"confidence":"High","gaps":["Whether phenotypes arise from import loss, cardiolipin loss, or both not separated","In vivo cardiac consequences not modeled"]},{"year":2025,"claim":"Identified a quality-control axis showing the Lon/Pim1 matrix protease degrades Pam18 and regulates its proteostasis, adding a layer of post-translational control over motor J-protein levels.","evidence":"In vitro degradation with purified Lon/Pim1 and in vivo Δpim1 yeast genetics with overexpression","pmids":["41099349"],"confidence":"Medium","gaps":["Conservation of Lon-mediated turnover for human DNAJC19 not shown","Physiological signals triggering degradation undefined"]},{"year":null,"claim":"How DNAJC19's matrix import function and its prohibitin/cardiolipin remodeling function are mechanistically integrated, and which loss best explains DCMA pathology, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure or biochemical reconstitution of the DNAJC19-prohibitin-tafazzin module","Causal hierarchy among import defect, cardiolipin defect, and cardiomyopathy not established","Human-specific functional import assays largely absent"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0,1,4]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,1,9]},{"term_id":"GO:0044183","term_label":"protein folding chaperone","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[0,2,12]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0,5]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[0,6]},{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[10,12]}],"complexes":["TIM23 presequence translocase import motor (PAM)","Tim14/Pam18-Tim16/Pam16 heterodimer","prohibitin (PHB) membrane domain complex"],"partners":["TIMM16","MTHSP70","TIMM44","TIMM17","PHB2","LONP1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96DA6","full_name":"Mitochondrial import inner membrane translocase subunit TIM14","aliases":["DnaJ homolog subfamily C member 19"],"length_aa":116,"mass_kda":12.5,"function":"Mitochondrial co-chaperone which forms a complex with prohibitins to regulate cardiolipin remodeling (By similarity). May be a component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner. May act as a co-chaperone that stimulate the ATP-dependent activity (By similarity)","subcellular_location":"Mitochondrion inner membrane","url":"https://www.uniprot.org/uniprotkb/Q96DA6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DNAJC19","classification":"Not Classified","n_dependent_lines":347,"n_total_lines":1208,"dependency_fraction":0.28725165562913907},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/DNAJC19","total_profiled":1310},"omim":[{"mim_id":"614336","title":"PRESEQUENCE TRANSLOCASE-ASSOCIATED MOTOR 16; PAM16","url":"https://www.omim.org/entry/614336"},{"mim_id":"610198","title":"3-@METHYLGLUTACONIC ACIDURIA, TYPE V; MGCA5","url":"https://www.omim.org/entry/610198"},{"mim_id":"608977","title":"DNAJ/HSP40 HOMOLOG, SUBFAMILY C, MEMBER 19; DNAJC19","url":"https://www.omim.org/entry/608977"},{"mim_id":"250950","title":"3-@METHYLGLUTACONIC ACIDURIA, TYPE I; MGCA1","url":"https://www.omim.org/entry/250950"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DNAJC19"},"hgnc":{"alias_symbol":["TIMM14","Tim14","Pam18"],"prev_symbol":[]},"alphafold":{"accession":"Q96DA6","domains":[{"cath_id":"1.10.287.110","chopping":"59-112","consensus_level":"high","plddt":96.8806,"start":59,"end":112},{"cath_id":"1.20.5","chopping":"1-35","consensus_level":"medium","plddt":80.3811,"start":1,"end":35}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96DA6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96DA6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96DA6-F1-predicted_aligned_error_v6.png","plddt_mean":87.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DNAJC19","jax_strain_url":"https://www.jax.org/strain/search?query=DNAJC19"},"sequence":{"accession":"Q96DA6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96DA6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96DA6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96DA6"}},"corpus_meta":[{"pmid":"16055927","id":"PMC_16055927","title":"Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-like condition.","date":"2005","source":"Journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/16055927","citation_count":186,"is_preprint":false},{"pmid":"24856930","id":"PMC_24856930","title":"DNAJC19, a mitochondrial cochaperone associated with cardiomyopathy, forms a complex with prohibitins to regulate cardiolipin remodeling.","date":"2014","source":"Cell metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/24856930","citation_count":174,"is_preprint":false},{"pmid":"14517234","id":"PMC_14517234","title":"Tim14, a novel key component of the import motor of the TIM23 protein translocase of mitochondria.","date":"2003","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/14517234","citation_count":168,"is_preprint":false},{"pmid":"16977310","id":"PMC_16977310","title":"Structure and function of Tim14 and Tim16, the J and J-like components of the mitochondrial protein import motor.","date":"2006","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/16977310","citation_count":99,"is_preprint":false},{"pmid":"15218029","id":"PMC_15218029","title":"The presequence translocase-associated protein import motor of mitochondria. Pam16 functions in an antagonistic manner to Pam18.","date":"2004","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15218029","citation_count":98,"is_preprint":false},{"pmid":"22797137","id":"PMC_22797137","title":"New mutation of mitochondrial DNAJC19 causing dilated and noncompaction cardiomyopathy, anemia, ataxia, and male genital anomalies.","date":"2012","source":"Pediatric research","url":"https://pubmed.ncbi.nlm.nih.gov/22797137","citation_count":79,"is_preprint":false},{"pmid":"18003975","id":"PMC_18003975","title":"Interaction of the J-protein heterodimer Pam18/Pam16 of the mitochondrial import motor with the translocon of the inner membrane.","date":"2007","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/18003975","citation_count":67,"is_preprint":false},{"pmid":"17452317","id":"PMC_17452317","title":"Association of the Tim14.Tim16 subcomplex with the TIM23 translocase is crucial for function of the 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(DCMA) caused by a homozygous DNAJC19 mutation.","date":"2020","source":"Stem cell research","url":"https://pubmed.ncbi.nlm.nih.gov/32521499","citation_count":6,"is_preprint":false},{"pmid":"39146359","id":"PMC_39146359","title":"Pam16 and Pam18 were repurposed during Trypanosoma brucei evolution to regulate the replication of mitochondrial DNA.","date":"2024","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/39146359","citation_count":3,"is_preprint":false},{"pmid":"41099349","id":"PMC_41099349","title":"Lon/Pim1-mediated degradation of presequence translocase-associated motor components Pam16 and Pam18 in Saccharomyces cerevisiae.","date":"2025","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/41099349","citation_count":1,"is_preprint":false},{"pmid":"38696852","id":"PMC_38696852","title":"Generation of a homozygous DNAJC19 knockout human embryonic stem cell line by CRISPR/Cas9 system.","date":"2024","source":"Stem cell research","url":"https://pubmed.ncbi.nlm.nih.gov/38696852","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12639,"output_tokens":3420,"usd":0.044609,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11040,"output_tokens":3971,"usd":0.077238,"stage2_stop_reason":"end_turn"},"total_usd":0.121847,"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\": 2003,\n      \"finding\": \"Tim14 (DNAJC19 yeast ortholog) is an integral inner mitochondrial membrane protein with a J-domain exposed to the matrix; it is an essential component of the TIM23 import motor, stimulates the ATPase activity of mtHsp70, and interacts with Tim44 and mtHsp70 in an ATP-dependent manner. Mutation of the HPD motif of the J-domain is lethal.\",\n      \"method\": \"Genetic depletion in yeast, mitochondrial protein import assays, co-immunoprecipitation, HPD motif mutagenesis\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal methods (depletion, import assays, Co-IP, mutagenesis) in a single rigorous study establishing essential function\",\n      \"pmids\": [\"14517234\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Pam18 (DNAJC19 yeast ortholog) forms a complex with Pam16; Pam16 specifically antagonizes/inhibits Pam18-mediated stimulation of mtHsp70 ATPase activity. Pam16 lacking the HPD motif cannot stimulate mtHsp70 but can still inhibit Pam18.\",\n      \"method\": \"In vitro ATPase stimulation assays, genetic complementation in yeast, biochemical inhibition assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro ATPase assays combined with in vivo genetic complementation and mutagenesis\",\n      \"pmids\": [\"15218029\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"DNAJC19 is localized to mitochondria (inner mitochondrial membrane) in cardiac myocytes and shares sequence/organizational similarity with yeast Tim14 and Mdj2. A splice-site mutation (IVS3-1 G→C) causing DCMA syndrome was identified, establishing DNAJC19 as a component of the mitochondrial protein import pathway.\",\n      \"method\": \"Homozygosity mapping, mutation sequencing, RT-PCR, bioinformatics\",\n      \"journal\": \"Journal of medical genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic mapping and sequence analysis with prior localization data; mechanism inferred by homology to yeast proteins\",\n      \"pmids\": [\"16055927\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"The yeast import motor contains two J-proteins, Tim14 and Mdj2; Mdj2 forms a complex with Tim16, is recruited to TIM23 translocase, and stimulates mtHsp70 ATPase to the same extent as Tim14. Overexpressed Mdj2 fully rescues Tim14-null growth defect.\",\n      \"method\": \"Yeast genetics (deletion strains), biochemical co-purification, ATPase stimulation assays, overexpression complementation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal biochemical and genetic methods in a single study\",\n      \"pmids\": [\"16027163\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Crystal structure of the Tim14-Tim16 (Pam18-Pam16) complex shows the conserved domains have virtually identical folds but completely different surfaces. Tim16 tightly regulates the cochaperone activity of Tim14. Mutations destroying the Tim14-Tim16 complex are lethal.\",\n      \"method\": \"X-ray crystallography, mutagenesis, in vitro ATPase activity assays, yeast viability assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure combined with mutagenesis and functional assays in a single rigorous study\",\n      \"pmids\": [\"16977310\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"The Pam18:Pam16 heterodimer associates with the TIM23 translocon via three interactions: the N-terminus of Pam16 with the matrix side of the translocon, the IMS domain of Pam18 with Tim17, and direct J-domain:J-like-domain interaction. Pam16 plays the major role in translocon association; disruption of heterodimer stability dramatically reduces Pam18 (but not Pam16) association with the translocon.\",\n      \"method\": \"Biochemical co-purification, yeast genetic suppressor screen, domain deletion/mutagenesis, co-immunoprecipitation\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal biochemical assays, suppressor screen, domain mapping, multiple orthogonal methods\",\n      \"pmids\": [\"18003975\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"The hydrophobic N-terminal segment of Tim16 (yeast Pam16) is crucial for interaction of the Tim14·Tim16 complex with the core TIM23 translocase. Deletion of hydrophobic segments from both Tim16 and Tim14 is lethal; deletion of either alone causes growth defects and decreased matrix-protein import.\",\n      \"method\": \"Yeast genetics (deletion mutants), mitochondrial import assays, co-immunoprecipitation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic and biochemical complementation with import assays and Co-IP\",\n      \"pmids\": [\"17452317\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"The Pam18/Tim14-Pam16/Tim16 heterodimer is thermally more stable (Tm ~41°C) than either individual subunit (Tm 16.5°C and 29°C respectively), demonstrating stabilization upon complex formation.\",\n      \"method\": \"CD spectroscopy, chemical crosslinking (DSS), thermal denaturation, in vitro co-overexpression and purification\",\n      \"journal\": \"Protein science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro structural characterization by a single lab with clear biophysical methods but no functional readout beyond stability\",\n      \"pmids\": [\"17242434\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"The soluble domains of human DNAJC19 (Tim14/Pam18) and human Tim16/Pam16 interact with their yeast counterparts, forming heterodimeric complexes, and these hybrid complexes interact with yeast mtHsp70, demonstrating structural conservation across species.\",\n      \"method\": \"Recombinant protein purification, in vitro binding assays, cross-species heterodimer formation\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro reconstitution of heterodimer and mtHsp70 interaction, single lab, two orthogonal methods\",\n      \"pmids\": [\"19564938\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"The Pam18:Pam16 heterodimer interaction is required for physical tethering of Pam18 to the TIM23 translocon (via Pam16) rather than primarily for inhibiting Pam18's ATPase-stimulatory activity; a previously uncharacterized region of Pam16 is required for forming an active Pam18:Pam16 complex that can stimulate mtHsp70 ATPase activity.\",\n      \"method\": \"Biochemical ATPase assays, genetic interaction analysis, in vivo yeast complementation, domain mapping\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — biochemical and genetic assays in a single lab; partially revises prior model with multiple methods\",\n      \"pmids\": [\"22031295\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"DNAJC19 forms a complex with prohibitin (PHB) complexes in the inner mitochondrial membrane. Loss of DNAJC19 or PHB2 leads to impaired cell growth, defective cristae morphogenesis, and accumulation of cardiolipin species with altered acyl chains. PHB/DNAJC19 membrane domains regulate cardiolipin remodeling by tafazzin.\",\n      \"method\": \"PHB2 interactome mass spectrometry, Co-immunoprecipitation, cell growth assays, cardiolipin lipidomic analysis, gene knockout/knockdown\",\n      \"journal\": \"Cell metabolism\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — interactome MS, reciprocal Co-IP, lipidomics, and cellular phenotypic assays across multiple conditions in a single study\",\n      \"pmids\": [\"24856930\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Disruption of the Pam16-Pam18 heterodimer causes redistribution of Pam18 to respiratory chain supercomplexes where it forms a homodimer; this redistribution decreases protein import into mitochondria but stimulates mtHsp70-dependent assembly of respiratory chain complexes, revealing a dual function of the Pam16-Pam18 module.\",\n      \"method\": \"Yeast genetics, co-immunoprecipitation, mitochondrial protein import assays, respiratory chain complex assembly assays\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (Co-IP, import assays, assembly assays, genetics) in a single study establishing dual localization and function\",\n      \"pmids\": [\"35385740\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Loss of the DnaJ interaction domain in DNAJC19 (truncation variant) causes mitochondrial fragmentation, abnormal cristae formation, reduced mitochondrial protein expression, increased oxygen consumption rate, altered substrate utilization (decreased fatty acid uptake, increased glucose utilization), elevated ROS, increased mitochondrial membrane potential, and dysregulated Ca2+ kinetics in iPSC-derived cardiomyocytes.\",\n      \"method\": \"iPSC-derived cardiomyocyte models (patient-derived and CRISPR gene-edited), electron microscopy, Seahorse respirometry, radioactive tracer uptake assays, ROS measurements, Ca2+ imaging, sarcomere shortening analysis\",\n      \"journal\": \"Molecular metabolism\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — patient-derived and gene-edited cell models with multiple orthogonal functional assays in a single study\",\n      \"pmids\": [\"38142971\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Pam18 (DNAJC19 yeast ortholog) is specifically targeted for degradation by the Lon/Pim1 mitochondrial matrix protease both in vitro and in vivo; overexpression of Pam18 exacerbates growth defects in Δpim1 cells, establishing Lon/Pim1 as a regulator of Pam18 protein homeostasis.\",\n      \"method\": \"In vitro degradation assays with purified Lon/Pim1, in vivo yeast genetics (Δpim1 strain), overexpression studies\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — in vitro and in vivo assays in single lab, two orthogonal approaches\",\n      \"pmids\": [\"41099349\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DNAJC19 (Tim14/Pam18) is an inner mitochondrial membrane J-protein that, as part of the TIM23 presequence translocase-associated motor, stimulates the ATPase activity of mtHsp70 to drive ATP-dependent protein import into the mitochondrial matrix; it forms an essential heterodimer with the J-like protein Tim16/Pam16—whose crystal structure has been solved—which regulates DNAJC19's cochaperone activity and tethers it to the translocon via Tim17 and Tim44 interactions; additionally, DNAJC19 forms a complex with prohibitins in the inner membrane to regulate tafazzin-mediated cardiolipin remodeling, and loss of its DnaJ domain causes mitochondrial fragmentation, cristae defects, altered cardiolipin acylation, and metabolic dysfunction underlying dilated cardiomyopathy with ataxia (DCMA) syndrome.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DNAJC19 (Tim14/Pam18) is an inner mitochondrial membrane J-protein that functions as the essential J-domain cochaperone of the TIM23 presequence translocase-associated import motor, stimulating the ATPase activity of mtHsp70 to drive ATP-dependent translocation of precursor proteins into the matrix [#0]. Its activity is governed by an obligate heterodimer with the J-like protein Tim16/Pam16: structural and biochemical work shows the two share nearly identical folds but distinct surfaces, with Tim16 tightly regulating DNAJC19's cochaperone output, and disruption of the complex being lethal [#1, #4]. Heterodimer formation also stabilizes both subunits and tethers DNAJC19 to the translocon, where Tim16 makes the major contacts via its N-terminal hydrophobic segment and the matrix face of the channel while the DNAJC19 IMS domain engages Tim17, so that loss of heterodimer integrity strips DNAJC19 from the translocon and impairs matrix import [#5, #6, #7]. Beyond import, DNAJC19 has a second function: it associates with prohibitin (PHB) membrane domains in the inner membrane to organize tafazzin-mediated cardiolipin remodeling, and its loss produces defective cristae morphogenesis and accumulation of cardiolipin species with altered acyl chains [#10]. Truncation removing the DnaJ interaction domain causes mitochondrial fragmentation, abnormal cristae, altered substrate utilization, elevated ROS and dysregulated Ca2+ handling in cardiomyocytes [#12]. A splice-site mutation in DNAJC19 causes dilated cardiomyopathy with ataxia (DCMA) syndrome [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Established that the yeast ortholog Tim14 is an essential matrix-facing J-protein of the TIM23 import motor that drives mtHsp70-powered protein import, defining the core molecular activity of this protein family.\",\n      \"evidence\": \"Genetic depletion, import assays, Co-IP, and HPD-motif mutagenesis in yeast\",\n      \"pmids\": [\"14517234\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not address regulation of J-domain activity by partner subunits\", \"Human ortholog not directly characterized\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Identified the regulatory partner Pam16 and showed it antagonizes Pam18-mediated mtHsp70 ATPase stimulation, revealing that cochaperone output is held in check by a J-like partner.\",\n      \"evidence\": \"In vitro ATPase assays, genetic complementation, and HPD-mutant inhibition assays in yeast\",\n      \"pmids\": [\"15218029\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the Pam16 antagonism not resolved\", \"Whether inhibition operates at the translocon in vivo not yet defined\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Connected the gene to human disease, localizing DNAJC19 to the cardiac inner mitochondrial membrane and identifying a splice-site mutation causing DCMA syndrome.\",\n      \"evidence\": \"Homozygosity mapping, mutation sequencing, RT-PCR, and bioinformatics\",\n      \"pmids\": [\"16055927\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism inferred by homology to yeast Tim14 rather than direct human assays\", \"Did not establish how import defect produces cardiomyopathy\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Showed the motor harbors a second J-protein, Mdj2, that can functionally substitute for Tim14, refining understanding of J-protein redundancy at the translocon.\",\n      \"evidence\": \"Yeast deletion strains, co-purification, ATPase assays, and overexpression complementation\",\n      \"pmids\": [\"16027163\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological role of two J-proteins not delineated\", \"No mammalian counterpart of this redundancy described\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Provided the structural basis for heterodimer-regulated cochaperone activity by solving the Tim14-Tim16 complex, showing identical folds with divergent surfaces and lethal phenotypes upon complex disruption.\",\n      \"evidence\": \"X-ray crystallography with mutagenesis, ATPase assays, and yeast viability tests\",\n      \"pmids\": [\"16977310\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structure of the full translocon-bound module not resolved\", \"Human complex structure not determined\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Defined how the heterodimer docks onto the translocon, mapping three interactions and assigning Tim16 the dominant tethering role via its hydrophobic N-terminus, and showed heterodimer formation thermally stabilizes both subunits.\",\n      \"evidence\": \"Co-purification, suppressor screens, domain mapping, import assays, CD spectroscopy and crosslinking in yeast\",\n      \"pmids\": [\"18003975\", \"17452317\", \"17242434\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Dynamics of docking during active import not captured\", \"Quantitative contribution of each contact to import flux unresolved\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Demonstrated cross-species conservation by showing human DNAJC19 and human Tim16 form heterodimers and engage mtHsp70 even when paired with yeast counterparts, extending the yeast model to the human proteins.\",\n      \"evidence\": \"Recombinant protein purification and in vitro cross-species heterodimer binding assays\",\n      \"pmids\": [\"19564938\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional import assay in human mitochondria\", \"Native human translocon context not tested\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Revised the regulatory model, showing the Pam18:Pam16 interaction primarily serves to physically tether Pam18 to the translocon rather than to inhibit its activity, and identified a Pam16 region required to form an active stimulatory complex.\",\n      \"evidence\": \"ATPase assays, genetic interaction analysis, and domain mapping in yeast\",\n      \"pmids\": [\"22031295\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Reconciliation with the earlier antagonism model not fully settled\", \"Region of Pam16 not structurally defined\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Uncovered a second, import-independent function by showing DNAJC19 partners with prohibitin domains to regulate tafazzin-mediated cardiolipin remodeling and cristae morphology, linking it directly to membrane lipid homeostasis.\",\n      \"evidence\": \"PHB2 interactome MS, reciprocal Co-IP, cardiolipin lipidomics, and knockout/knockdown phenotyping\",\n      \"pmids\": [\"24856930\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular mechanism by which DNAJC19 controls tafazzin not defined\", \"Relationship between import role and cardiolipin role unresolved\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Revealed a moonlighting function in which heterodimer disruption redistributes Pam18 to respiratory chain supercomplexes as a homodimer, where it promotes mtHsp70-dependent complex assembly at the cost of import.\",\n      \"evidence\": \"Yeast genetics, Co-IP, import assays, and respiratory chain assembly assays\",\n      \"pmids\": [\"35385740\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether human DNAJC19 shares this dual localization not tested\", \"Trigger for physiological redistribution unknown\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Connected the disease truncation to cellular phenotype, showing loss of the DnaJ interaction domain drives mitochondrial fragmentation, cristae defects, metabolic reprogramming, ROS elevation and Ca2+ dysregulation in cardiomyocytes.\",\n      \"evidence\": \"Patient-derived and CRISPR-edited iPSC-cardiomyocytes with EM, Seahorse respirometry, tracer uptake, ROS and Ca2+ imaging\",\n      \"pmids\": [\"38142971\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether phenotypes arise from import loss, cardiolipin loss, or both not separated\", \"In vivo cardiac consequences not modeled\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identified a quality-control axis showing the Lon/Pim1 matrix protease degrades Pam18 and regulates its proteostasis, adding a layer of post-translational control over motor J-protein levels.\",\n      \"evidence\": \"In vitro degradation with purified Lon/Pim1 and in vivo Δpim1 yeast genetics with overexpression\",\n      \"pmids\": [\"41099349\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Conservation of Lon-mediated turnover for human DNAJC19 not shown\", \"Physiological signals triggering degradation undefined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How DNAJC19's matrix import function and its prohibitin/cardiolipin remodeling function are mechanistically integrated, and which loss best explains DCMA pathology, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structure or biochemical reconstitution of the DNAJC19-prohibitin-tafazzin module\", \"Causal hierarchy among import defect, cardiolipin defect, and cardiomyopathy not established\", \"Human-specific functional import assays largely absent\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 1, 9]},\n      {\"term_id\": \"GO:0044183\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005743\", \"supporting_discovery_ids\": [0, 2, 10]},\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0, 2, 12]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 5]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 6]},\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [10, 12]}\n    ],\n    \"complexes\": [\n      \"TIM23 presequence translocase import motor (PAM)\",\n      \"Tim14/Pam18-Tim16/Pam16 heterodimer\",\n      \"prohibitin (PHB) membrane domain complex\"\n    ],\n    \"partners\": [\n      \"TIMM16\",\n      \"mtHsp70\",\n      \"TIMM44\",\n      \"TIMM17\",\n      \"PHB2\",\n      \"LONP1\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":6,"faith_pct":83.33333333333333}}