{"gene":"SLC25A51","run_date":"2026-06-10T07:46:32","timeline":{"discoveries":[{"year":2020,"finding":"SLC25A51 (MCART1) is a mammalian mitochondrial NAD+ transporter: loss of SLC25A51 decreases mitochondrial (but not whole-cell) NAD+ content and blocks NAD+ uptake into isolated mitochondria; overexpression of SLC25A51 or its paralogue SLC25A52 increases mitochondrial NAD+ levels and restores NAD+ uptake into yeast mitochondria lacking endogenous NAD+ transporters.","method":"NAD+ measurement in isolated mitochondria, NAD+ uptake assays in isolated mitochondria from KO/OE cells, functional complementation in yeast lacking endogenous NAD+ transporters, loss-of-function respiratory phenotype","journal":"Nature","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal methods (mitochondrial NAD+ quantification, in vitro uptake into isolated mitochondria, yeast complementation) in one rigorous study, independently replicated by two concurrent papers (PMIDs 33087354, 33262325)","pmids":["32906142"],"is_preprint":false},{"year":2020,"finding":"MCART1/SLC25A51 loss causes large decreases in TCA cycle flux, mitochondrial respiration, ETC complex I activity, and mitochondrial NAD+/NADH levels; isolated mitochondria from MCART1-null cells show greatly decreased NAD uptake in vitro, while overexpression increases it; MCART1 and yeast NDT1 can functionally complement each other.","method":"MCART1-null cell lines, TCA cycle flux analysis, Seahorse respirometry, ETC complex I activity assay, in vitro NAD uptake into isolated mitochondria, yeast functional complementation, gene essentiality co-essentiality mining","journal":"Science advances","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal functional assays (metabolic flux, respiration, complex I activity, in vitro uptake, cross-species complementation), independent replication of NAD+ transport function","pmids":["33087354"],"is_preprint":false},{"year":2020,"finding":"Genetic interaction network analysis placed SLC25A51 as an enabler of mitochondrial NAD import, with strong genetic interactions linking it to mitochondrial respiration and redox metabolism; metabolomics and genomics confirmed its role in NAD import.","method":"Genetic interaction mapping across SLC genes, metabolomics, genomics, epistasis analysis","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — epistasis-driven approach with metabolomics validation, independently confirming findings from two concurrent papers","pmids":["33262325"],"is_preprint":false},{"year":2023,"finding":"SLC25A51 selectively transports oxidized NAD+ (not NADH); cardiolipin binds to three distinct exterior sites on SLC25A51 and mutations at these sites impair both cardiolipin binding and transporter activity; a single salt bridge controls matrix gate formation; an electrostatic interaction between the charged nicotinamide ring of NAD+ and a negatively charged pore patch governs selectivity; interior residue E132 interacts with NAD+ to dynamically weaken the salt bridge gate, initiating ligand-led transport.","method":"Molecular dynamics simulations with reconstitution into lipid bilayers, site-directed mutagenesis of cardiolipin-binding sites and gating residues, functional transport assays","journal":"EMBO reports","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — MD simulation plus mutagenesis and functional assays in single study; abstract does not report independent replication","pmids":["37575034"],"is_preprint":false},{"year":2022,"finding":"Knockdown of Slc25a51 in hepatocytes and mouse liver decreases mitochondrial NAD+ levels and reduces SIRT3 deacetylase activity, evidenced by increased acetylation of SIRT3 target proteins IDH2 and ACADL; Slc25a51 knockdown also reduces mitochondrial oxygen consumption rate; fasting induces hepatic Slc25a51 expression and its circadian expression is disrupted in BMAL1 liver-specific knockout mice.","method":"shRNA-mediated knockdown in hepatocytes and mouse liver, mitochondrial NAD+ quantification, SIRT3 target acetylation (IDH2, ACADL) by western blot, Seahorse mitochondrial OCR, liver-specific BMAL1 KO mice","journal":"Metabolism: clinical and experimental","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KD with defined molecular phenotypes (SIRT3 substrate acetylation, OCR) and in vivo mouse model, single lab","pmids":["35932995"],"is_preprint":false},{"year":2023,"finding":"Loss of SLC25A51 elevates mitochondrial protein acetylation due to SIRT3 dysfunction, which impairs P5CS enzymatic activity (the key enzyme in proline biosynthesis) and reduces intracellular proline content; fludarabine phosphate binds to and inhibits SLC25A51, causing mitochondrial NAD+ decrease and protein hyperacetylation.","method":"SLC25A51 KO cell lines, mitochondrial protein acetylation assays, P5CS enzymatic activity assay, proline quantification, drug-binding assay with fludarabine phosphate, cell proliferation assays","journal":"Cell death and differentiation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO with defined enzymatic readouts (P5CS activity, acetylation), drug-binding experiment; single lab","pmids":["37419986"],"is_preprint":false},{"year":2023,"finding":"Absence of SLC25A51 leads to increased NAD+ concentration in both cytoplasm and nucleus (not due to upregulation of the salvage pathway), resulting in increased PARP1-mediated nuclear ADP-ribosylation, faster repair of single-strand DNA lesions, reduced PARP1 chromatin retention, and decreased sensitivity to PARP inhibitors in breast cancer cells.","method":"SLC25A51 KO cells, subcellular NAD+ measurement, ADP-ribosylation assays, single-strand DNA damage repair assays, PARP1 chromatin retention assay, PARP inhibitor sensitivity assays","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO with multiple functional readouts (NAD+ compartmentalization, ADP-ribosylation, DNA repair, drug sensitivity), single lab","pmids":["37587695"],"is_preprint":false},{"year":2024,"finding":"SLC25A51 selectively imports oxidized NAD+ into the mitochondrial matrix; depletion of SLC25A51 in AML cells shunts metabolic flux away from mitochondrial oxidative pathways without increasing glycolytic flux, and decouples the mitochondrial NAD+/NADH ratio, indicating that AML cells upregulate SLC25A51 to sustain oxidative reactions from multiple fuels for a proliferative advantage.","method":"Metabolic flux analysis (isotope tracing), SLC25A51 depletion by shRNA, orthotopic xenograft models, apoptosis assays, combination treatment with 5-azacytidine in vivo","journal":"Cell metabolism","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — metabolic flux analysis with KD and in vivo model, single lab","pmids":["38354740"],"is_preprint":false},{"year":2025,"finding":"BACH1 transcriptionally represses SLC25A51; BACH1 deficiency activates SLC25A51 transcription (confirmed by dual-luciferase reporter and EMSA), promoting mitochondrial NAD+ transport and restoring ETC complex I, II, and IV activities; shRNA knockdown of SLC25A51 reverses the pro-proliferative effect of BACH1 deficiency on endothelial cells.","method":"Dual-luciferase reporter assay, EMSA, BACH1-knockout mice, shRNA knockdown of SLC25A51, ETC complex activity assays, HUVEC proliferation assays, proteomics/transcriptomics","journal":"Molecular medicine (Cambridge, Mass.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — transcriptional regulation confirmed by reporter assay and EMSA, functional rescue experiment; single lab","pmids":["40312332"],"is_preprint":false},{"year":2026,"finding":"KRAS-mutant AML cells exhibit reduced 2-oxoglutarate dehydrogenase complex (OGDHC)-mediated succinylation of SLC25A51 at K264, a modification that stabilizes the transporter; reduced succinylation destabilizes SLC25A51, creating a synthetic lethal vulnerability exploited by compound 615, which inhibits SLC25A51 and succinate dehydrogenase simultaneously to cause catastrophic mitochondrial NAD+ depletion specifically in KRAS-mutant cells.","method":"Mass spectrometry identification of K264 succinylation, mutagenesis, compound 615 treatment, SLC25A51 stability assays, mitochondrial NAD+ measurement, in vivo AML models","journal":"Cell metabolism","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — PTM site identified by MS with functional mutagenesis and mechanistic follow-up; single lab, abstract-level description","pmids":["41616775"],"is_preprint":false},{"year":2025,"finding":"Overexpression of SLC25A51 (but not a transport-dead mutant) induces senescence markers in beta cells; beta-cell-specific deletion of SLC25A51 reduces p16INK4a levels, lowers circulating insulin and glucose levels, and improves insulin sensitivity; NRF2 is implicated as a transcriptional regulator of SLC25A51 upregulation during senescence.","method":"Beta-cell-specific Slc25a51 KO mice, SLC25A51 overexpression with transport-dead mutant control, p16INK4a measurement, glucose/insulin tolerance tests, senescence markers","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — transport-dead mutant control distinguishes transporter activity from other effects; preprint, not yet peer-reviewed","pmids":["40642112"],"is_preprint":true},{"year":2026,"finding":"Adipocyte-specific deletion of Slc25a51 markedly reduces adipose tissue mitochondrial NAD+ levels and impairs mitochondrial respiratory function, fatty acid oxidation capacity, and adiponectin production, leading to age-associated obesity, insulin resistance, and hepatosteatosis; adipocyte-specific overexpression protects against obesity and insulin resistance caused by aging.","method":"Adipocyte-specific Slc25a51 KO and OE mouse models, mitochondrial NAD+ quantification, respirometry, fatty acid oxidation assays, adiponectin measurement, metabolic phenotyping","journal":"Aging cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — tissue-specific KO and OE with multiple orthogonal metabolic readouts; single lab","pmids":["42015379"],"is_preprint":false}],"current_model":"SLC25A51 (MCART1) is the mammalian mitochondrial inner-membrane NAD+ transporter that selectively imports oxidized NAD+ into the mitochondrial matrix; it operates via a cardiolipin-assisted, ligand-induced mechanism in which NAD+ engages a negatively charged pore patch and residue E132 to weaken a salt-bridge gate, enabling transport; by controlling mitochondrial NAD+ availability, SLC25A51 sustains TCA cycle flux, ETC complex I activity, and oxidative phosphorylation, and is required for NAD+-dependent sirtuin (SIRT3) deacetylase activity in mitochondria, with its protein stability regulated by OGDHC-mediated K264 succinylation and its transcription regulated by BACH1."},"narrative":{"mechanistic_narrative":"SLC25A51 (MCART1) is the mammalian mitochondrial inner-membrane carrier that selectively imports oxidized NAD+ into the mitochondrial matrix, establishing the supply of NAD+ that drives mitochondrial redox metabolism [PMID:32906142, PMID:33087354]. Its identity as a NAD+ transporter rests on convergent evidence: loss of SLC25A51 selectively depletes mitochondrial (not whole-cell) NAD+ and abolishes NAD+ uptake into isolated mitochondria, while overexpression of SLC25A51 or its paralogue SLC25A52 restores uptake and rescues yeast mitochondria lacking endogenous NAD+ transporters [PMID:32906142]. By controlling matrix NAD+ availability, SLC25A51 sustains TCA cycle flux, ETC complex I activity, and mitochondrial respiration [PMID:33087354], and AML cells upregulate it to maintain oxidative metabolism from multiple fuels [PMID:38354740]. Mechanistically, transport is cardiolipin-assisted and ligand-led: cardiolipin engages three exterior sites required for activity, an electrostatic interaction between the nicotinamide ring and a negatively charged pore patch governs selectivity for NAD+ over NADH, and interior residue E132 weakens a salt-bridge matrix gate to initiate transport [PMID:37575034]. Downstream, matrix NAD+ delivered by SLC25A51 is required for SIRT3 deacetylase activity, so its loss elevates mitochondrial protein acetylation, impairing SIRT3 targets including IDH2, ACADL, and the proline-biosynthetic enzyme P5CS [PMID:35932995, PMID:37419986]. Loss of mitochondrial import also redistributes NAD+ to the nucleus and cytoplasm, increasing PARP1-mediated ADP-ribosylation and single-strand break repair and reducing PARP-inhibitor sensitivity [PMID:37587695]. SLC25A51 abundance is set transcriptionally by repression from BACH1 [PMID:40312332] and post-translationally by OGDHC-mediated K264 succinylation that stabilizes the protein [PMID:41616775], and its activity influences cellular senescence and systemic metabolism in beta cells and adipose tissue [PMID:42015379].","teleology":[{"year":2020,"claim":"Established the long-sought identity of the mammalian mitochondrial NAD+ transporter, resolving how the matrix obtains NAD+ when no eukaryotic carrier had been defined.","evidence":"Mitochondrial NAD+ quantification, in vitro NAD+ uptake into isolated mitochondria, and functional complementation in yeast lacking endogenous NAD+ transporters in KO/OE cells","pmids":["32906142","33087354","33262325"],"confidence":"High","gaps":["Structural basis of transport not resolved at this stage","Did not define transport mechanism or selectivity determinants"]},{"year":2020,"claim":"Connected the transport function to downstream bioenergetics, showing that mitochondrial NAD+ import is rate-limiting for oxidative metabolism rather than a passive housekeeping process.","evidence":"TCA flux analysis, Seahorse respirometry, ETC complex I activity assays, and in vitro uptake in MCART1-null cells","pmids":["33087354"],"confidence":"High","gaps":["Did not address how transporter abundance is regulated","Tissue- and disease-specific roles not examined"]},{"year":2023,"claim":"Defined the molecular transport mechanism, explaining how the carrier achieves NAD+ selectivity and gates substrate passage across the inner membrane.","evidence":"Molecular dynamics simulations with lipid bilayer reconstitution plus site-directed mutagenesis of cardiolipin sites and gating residues with functional transport assays","pmids":["37575034"],"confidence":"Medium","gaps":["No experimental high-resolution structure reported","MD-derived gating model not independently replicated"]},{"year":2022,"claim":"Linked SLC25A51-supplied matrix NAD+ to SIRT3 function, establishing a regulatory consequence of import on mitochondrial protein acetylation in liver.","evidence":"shRNA knockdown in hepatocytes and mouse liver with mitochondrial NAD+ quantification, SIRT3-target acetylation (IDH2, ACADL) westerns, and OCR measurement","pmids":["35932995"],"confidence":"Medium","gaps":["Single lab","Direct demonstration that acetylation changes are SIRT3-dependent in vivo not fully resolved"]},{"year":2023,"claim":"Extended the SIRT3 axis to a specific metabolic output and identified a pharmacological inhibitor, showing import loss impairs proline biosynthesis via P5CS hyperacetylation.","evidence":"KO cell lines with P5CS enzymatic activity assay, acetylation and proline measurements, and fludarabine phosphate drug-binding assays","pmids":["37419986"],"confidence":"Medium","gaps":["Specificity of fludarabine phosphate for SLC25A51 versus other targets not fully delineated","Single lab"]},{"year":2023,"claim":"Revealed a cross-compartment consequence of transport loss, showing mitochondrial NAD+ import competes with nuclear NAD+-dependent PARP1 signaling and DNA repair.","evidence":"KO cells with subcellular NAD+ measurement, ADP-ribosylation and single-strand break repair assays, PARP1 chromatin retention, and PARP-inhibitor sensitivity in breast cancer cells","pmids":["37587695"],"confidence":"Medium","gaps":["Mechanism of NAD+ redistribution between compartments not fully defined","Single lab"]},{"year":2024,"claim":"Demonstrated a cancer dependency, showing AML cells upregulate SLC25A51 to sustain oxidative metabolism from multiple fuels.","evidence":"Isotope-tracing metabolic flux analysis with shRNA depletion, orthotopic xenografts, and combination treatment with 5-azacytidine in vivo","pmids":["38354740"],"confidence":"Medium","gaps":["Generalizability beyond AML not established","Single lab"]},{"year":2025,"claim":"Identified transcriptional control of the transporter, placing SLC25A51 under repression by BACH1 with functional consequences for endothelial proliferation.","evidence":"Dual-luciferase reporter, EMSA, BACH1-KO mice, shRNA rescue, and ETC complex activity assays in HUVECs","pmids":["40312332"],"confidence":"Medium","gaps":["Single lab","Whether BACH1 regulation operates in other tissues unknown"]},{"year":2026,"claim":"Defined post-translational control of transporter stability, identifying OGDHC-mediated K264 succinylation as a stabilizing modification exploited for synthetic lethality in KRAS-mutant AML.","evidence":"MS identification of K264 succinylation, mutagenesis, compound 615 treatment, stability and mitochondrial NAD+ assays, and in vivo AML models","pmids":["41616775"],"confidence":"Medium","gaps":["Single lab, abstract-level description","Selectivity of compound 615 between SLC25A51 and SDH not fully characterized"]},{"year":2026,"claim":"Established systemic physiological roles, showing SLC25A51 controls mitochondrial NAD+ and oxidative function in adipose tissue and beta cells with consequences for aging metabolism.","evidence":"Tissue-specific KO and OE mouse models with mitochondrial NAD+ quantification, respirometry, fatty acid oxidation, adiponectin, and senescence/metabolic phenotyping","pmids":["42015379","40642112"],"confidence":"Medium","gaps":["Beta-cell senescence findings remain a preprint not yet peer-reviewed","Mechanism linking NRF2 to SLC25A51 in senescence not fully resolved"]},{"year":null,"claim":"An experimental high-resolution structure of SLC25A51 in substrate-bound and gated states is still needed to confirm the MD-derived transport and selectivity model.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No experimental structure in the corpus","Conformational cycle of the carrier inferred only from simulation"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005215","term_label":"transporter activity","supporting_discovery_ids":[0,1,3,7]},{"term_id":"GO:0140104","term_label":"molecular carrier activity","supporting_discovery_ids":[0,3]}],"localization":[{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[1,7]},{"term_id":"R-HSA-382551","term_label":"Transport of small molecules","supporting_discovery_ids":[0,3]}],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9H1U9","full_name":"Mitochondrial nicotinamide adenine dinucleotide transporter SLC25A51","aliases":["Mitochondrial NAD(+) transporter SLC25A51","Mitochondrial carrier triple repeat protein 1","Solute carrier family 25 member 51"],"length_aa":297,"mass_kda":33.7,"function":"Mitochondrial membrane carrier protein that mediates the import of NAD(+) into mitochondria (PubMed:32906142, PubMed:33087354, PubMed:33262325). Mitochondrial NAD(+) is required for glycolysis and mitochondrial respiration (PubMed:32906142, PubMed:33087354, PubMed:33262325). Compared to SLC25A52, SLC25A51-mediated transport is essential for the import of NAD(+) in mitochondria (PubMed:32906142). The transport mechanism, uniport or antiport, its electrogenicity and substrate selectivity, remain to be elucidated","subcellular_location":"Mitochondrion inner membrane","url":"https://www.uniprot.org/uniprotkb/Q9H1U9/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SLC25A51","classification":"Not Classified","n_dependent_lines":88,"n_total_lines":1165,"dependency_fraction":0.07553648068669527},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/SLC25A51","total_profiled":1310},"omim":[{"mim_id":"619153","title":"SOLUTE CARRIER FAMILY 25 (MITOCHONDRIAL CARRIER, NAD+ TRANSPORTER), MEMBER 51; SLC25A51","url":"https://www.omim.org/entry/619153"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Mitochondria","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SLC25A51"},"hgnc":{"alias_symbol":["MGC14836","CG7943"],"prev_symbol":["MCART1"]},"alphafold":{"accession":"Q9H1U9","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H1U9","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H1U9-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H1U9-F1-predicted_aligned_error_v6.png","plddt_mean":82.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SLC25A51","jax_strain_url":"https://www.jax.org/strain/search?query=SLC25A51"},"sequence":{"accession":"Q9H1U9","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9H1U9.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9H1U9/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H1U9"}},"corpus_meta":[{"pmid":"32906142","id":"PMC_32906142","title":"SLC25A51 is a mammalian mitochondrial NAD+ transporter.","date":"2020","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/32906142","citation_count":245,"is_preprint":false},{"pmid":"33087354","id":"PMC_33087354","title":"MCART1/SLC25A51 is required for mitochondrial NAD transport.","date":"2020","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/33087354","citation_count":162,"is_preprint":false},{"pmid":"33262325","id":"PMC_33262325","title":"Epistasis-driven identification of SLC25A51 as a regulator of human mitochondrial NAD import.","date":"2020","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/33262325","citation_count":107,"is_preprint":false},{"pmid":"38354740","id":"PMC_38354740","title":"SLC25A51 decouples the mitochondrial NAD+/NADH ratio to control proliferation of AML cells.","date":"2024","source":"Cell metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/38354740","citation_count":33,"is_preprint":false},{"pmid":"35932995","id":"PMC_35932995","title":"The mitochondrial NAD+ transporter SLC25A51 is a fasting-induced gene affecting SIRT3 functions.","date":"2022","source":"Metabolism: clinical and experimental","url":"https://pubmed.ncbi.nlm.nih.gov/35932995","citation_count":29,"is_preprint":false},{"pmid":"35182732","id":"PMC_35182732","title":"Overexpression of SLC25A51 promotes hepatocellular carcinoma progression by driving aerobic glycolysis through activation of SIRT5.","date":"2022","source":"Free radical biology & medicine","url":"https://pubmed.ncbi.nlm.nih.gov/35182732","citation_count":28,"is_preprint":false},{"pmid":"37419986","id":"PMC_37419986","title":"SLC25A51 promotes tumor growth through sustaining mitochondria acetylation homeostasis and proline biogenesis.","date":"2023","source":"Cell death and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/37419986","citation_count":27,"is_preprint":false},{"pmid":"37587695","id":"PMC_37587695","title":"Absence of mitochondrial SLC25A51 enhances PARP1-dependent DNA repair by increasing nuclear NAD+ levels.","date":"2023","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/37587695","citation_count":22,"is_preprint":false},{"pmid":"37575034","id":"PMC_37575034","title":"Dynamics of SLC25A51 reveal preference for oxidized NAD+ and substrate led transport.","date":"2023","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/37575034","citation_count":15,"is_preprint":false},{"pmid":"40312332","id":"PMC_40312332","title":"BACH1 deficiency improves placental angiogenesis via SLC25A51-mediated mitochondrial NAD+ transport in intrahepatic cholestasis of pregnancy.","date":"2025","source":"Molecular medicine (Cambridge, Mass.)","url":"https://pubmed.ncbi.nlm.nih.gov/40312332","citation_count":3,"is_preprint":false},{"pmid":"33583303","id":"PMC_33583303","title":"Differential levels of CHMP2B, LLPH, and SLC25A51 proteins in secondary renal amyloidosis.","date":"2021","source":"Expert review of proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/33583303","citation_count":2,"is_preprint":false},{"pmid":"41616775","id":"PMC_41616775","title":"Dual targeting of SLC25A51 and succinate dehydrogenase selectively depletes mitochondrial NAD+ to eradicate KRAS-driven AML.","date":"2026","source":"Cell metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/41616775","citation_count":0,"is_preprint":false},{"pmid":"40642112","id":"PMC_40642112","title":"The mitochondrial NAD transporter SLC25A51 is a modulator of beta cell senescence and type 2 diabetes.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/40642112","citation_count":0,"is_preprint":false},{"pmid":"41493825","id":"PMC_41493825","title":"Nicotinamide riboside enhances liver regeneration via the MCART1/ASB3 axis in obesity-compromised rats.","date":"2026","source":"Hepatology communications","url":"https://pubmed.ncbi.nlm.nih.gov/41493825","citation_count":0,"is_preprint":false},{"pmid":"41639843","id":"PMC_41639843","title":"Targeting miR-4653-3p/SLC25A51/SIRT3 axis to induce synthetic lethality in ARID1A-deficient colorectal cancer via blockade of DNA repair.","date":"2026","source":"Journal of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/41639843","citation_count":0,"is_preprint":false},{"pmid":"42226663","id":"PMC_42226663","title":"SLC25A51 mRNA-LNP Armors T Cells with Mitochondrial Fitness in Cancer Treatment.","date":"2026","source":"ACS applied materials & interfaces","url":"https://pubmed.ncbi.nlm.nih.gov/42226663","citation_count":0,"is_preprint":false},{"pmid":"42015379","id":"PMC_42015379","title":"The Mitochondrial NAD Transporter SLC25A51 in Adipocytes Regulates Adipose Tissue Mitochondrial Function and Systemic Metabolism During Aging.","date":"2026","source":"Aging cell","url":"https://pubmed.ncbi.nlm.nih.gov/42015379","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10021,"output_tokens":3379,"usd":0.040374,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11070,"output_tokens":3444,"usd":0.070725,"stage2_stop_reason":"end_turn"},"total_usd":0.111099,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"SLC25A51 (MCART1) is a mammalian mitochondrial NAD+ transporter: loss of SLC25A51 decreases mitochondrial (but not whole-cell) NAD+ content and blocks NAD+ uptake into isolated mitochondria; overexpression of SLC25A51 or its paralogue SLC25A52 increases mitochondrial NAD+ levels and restores NAD+ uptake into yeast mitochondria lacking endogenous NAD+ transporters.\",\n      \"method\": \"NAD+ measurement in isolated mitochondria, NAD+ uptake assays in isolated mitochondria from KO/OE cells, functional complementation in yeast lacking endogenous NAD+ transporters, loss-of-function respiratory phenotype\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal methods (mitochondrial NAD+ quantification, in vitro uptake into isolated mitochondria, yeast complementation) in one rigorous study, independently replicated by two concurrent papers (PMIDs 33087354, 33262325)\",\n      \"pmids\": [\"32906142\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"MCART1/SLC25A51 loss causes large decreases in TCA cycle flux, mitochondrial respiration, ETC complex I activity, and mitochondrial NAD+/NADH levels; isolated mitochondria from MCART1-null cells show greatly decreased NAD uptake in vitro, while overexpression increases it; MCART1 and yeast NDT1 can functionally complement each other.\",\n      \"method\": \"MCART1-null cell lines, TCA cycle flux analysis, Seahorse respirometry, ETC complex I activity assay, in vitro NAD uptake into isolated mitochondria, yeast functional complementation, gene essentiality co-essentiality mining\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal functional assays (metabolic flux, respiration, complex I activity, in vitro uptake, cross-species complementation), independent replication of NAD+ transport function\",\n      \"pmids\": [\"33087354\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Genetic interaction network analysis placed SLC25A51 as an enabler of mitochondrial NAD import, with strong genetic interactions linking it to mitochondrial respiration and redox metabolism; metabolomics and genomics confirmed its role in NAD import.\",\n      \"method\": \"Genetic interaction mapping across SLC genes, metabolomics, genomics, epistasis analysis\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — epistasis-driven approach with metabolomics validation, independently confirming findings from two concurrent papers\",\n      \"pmids\": [\"33262325\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SLC25A51 selectively transports oxidized NAD+ (not NADH); cardiolipin binds to three distinct exterior sites on SLC25A51 and mutations at these sites impair both cardiolipin binding and transporter activity; a single salt bridge controls matrix gate formation; an electrostatic interaction between the charged nicotinamide ring of NAD+ and a negatively charged pore patch governs selectivity; interior residue E132 interacts with NAD+ to dynamically weaken the salt bridge gate, initiating ligand-led transport.\",\n      \"method\": \"Molecular dynamics simulations with reconstitution into lipid bilayers, site-directed mutagenesis of cardiolipin-binding sites and gating residues, functional transport assays\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — MD simulation plus mutagenesis and functional assays in single study; abstract does not report independent replication\",\n      \"pmids\": [\"37575034\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Knockdown of Slc25a51 in hepatocytes and mouse liver decreases mitochondrial NAD+ levels and reduces SIRT3 deacetylase activity, evidenced by increased acetylation of SIRT3 target proteins IDH2 and ACADL; Slc25a51 knockdown also reduces mitochondrial oxygen consumption rate; fasting induces hepatic Slc25a51 expression and its circadian expression is disrupted in BMAL1 liver-specific knockout mice.\",\n      \"method\": \"shRNA-mediated knockdown in hepatocytes and mouse liver, mitochondrial NAD+ quantification, SIRT3 target acetylation (IDH2, ACADL) by western blot, Seahorse mitochondrial OCR, liver-specific BMAL1 KO mice\",\n      \"journal\": \"Metabolism: clinical and experimental\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KD with defined molecular phenotypes (SIRT3 substrate acetylation, OCR) and in vivo mouse model, single lab\",\n      \"pmids\": [\"35932995\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Loss of SLC25A51 elevates mitochondrial protein acetylation due to SIRT3 dysfunction, which impairs P5CS enzymatic activity (the key enzyme in proline biosynthesis) and reduces intracellular proline content; fludarabine phosphate binds to and inhibits SLC25A51, causing mitochondrial NAD+ decrease and protein hyperacetylation.\",\n      \"method\": \"SLC25A51 KO cell lines, mitochondrial protein acetylation assays, P5CS enzymatic activity assay, proline quantification, drug-binding assay with fludarabine phosphate, cell proliferation assays\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO with defined enzymatic readouts (P5CS activity, acetylation), drug-binding experiment; single lab\",\n      \"pmids\": [\"37419986\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Absence of SLC25A51 leads to increased NAD+ concentration in both cytoplasm and nucleus (not due to upregulation of the salvage pathway), resulting in increased PARP1-mediated nuclear ADP-ribosylation, faster repair of single-strand DNA lesions, reduced PARP1 chromatin retention, and decreased sensitivity to PARP inhibitors in breast cancer cells.\",\n      \"method\": \"SLC25A51 KO cells, subcellular NAD+ measurement, ADP-ribosylation assays, single-strand DNA damage repair assays, PARP1 chromatin retention assay, PARP inhibitor sensitivity assays\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO with multiple functional readouts (NAD+ compartmentalization, ADP-ribosylation, DNA repair, drug sensitivity), single lab\",\n      \"pmids\": [\"37587695\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SLC25A51 selectively imports oxidized NAD+ into the mitochondrial matrix; depletion of SLC25A51 in AML cells shunts metabolic flux away from mitochondrial oxidative pathways without increasing glycolytic flux, and decouples the mitochondrial NAD+/NADH ratio, indicating that AML cells upregulate SLC25A51 to sustain oxidative reactions from multiple fuels for a proliferative advantage.\",\n      \"method\": \"Metabolic flux analysis (isotope tracing), SLC25A51 depletion by shRNA, orthotopic xenograft models, apoptosis assays, combination treatment with 5-azacytidine in vivo\",\n      \"journal\": \"Cell metabolism\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — metabolic flux analysis with KD and in vivo model, single lab\",\n      \"pmids\": [\"38354740\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"BACH1 transcriptionally represses SLC25A51; BACH1 deficiency activates SLC25A51 transcription (confirmed by dual-luciferase reporter and EMSA), promoting mitochondrial NAD+ transport and restoring ETC complex I, II, and IV activities; shRNA knockdown of SLC25A51 reverses the pro-proliferative effect of BACH1 deficiency on endothelial cells.\",\n      \"method\": \"Dual-luciferase reporter assay, EMSA, BACH1-knockout mice, shRNA knockdown of SLC25A51, ETC complex activity assays, HUVEC proliferation assays, proteomics/transcriptomics\",\n      \"journal\": \"Molecular medicine (Cambridge, Mass.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — transcriptional regulation confirmed by reporter assay and EMSA, functional rescue experiment; single lab\",\n      \"pmids\": [\"40312332\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"KRAS-mutant AML cells exhibit reduced 2-oxoglutarate dehydrogenase complex (OGDHC)-mediated succinylation of SLC25A51 at K264, a modification that stabilizes the transporter; reduced succinylation destabilizes SLC25A51, creating a synthetic lethal vulnerability exploited by compound 615, which inhibits SLC25A51 and succinate dehydrogenase simultaneously to cause catastrophic mitochondrial NAD+ depletion specifically in KRAS-mutant cells.\",\n      \"method\": \"Mass spectrometry identification of K264 succinylation, mutagenesis, compound 615 treatment, SLC25A51 stability assays, mitochondrial NAD+ measurement, in vivo AML models\",\n      \"journal\": \"Cell metabolism\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — PTM site identified by MS with functional mutagenesis and mechanistic follow-up; single lab, abstract-level description\",\n      \"pmids\": [\"41616775\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Overexpression of SLC25A51 (but not a transport-dead mutant) induces senescence markers in beta cells; beta-cell-specific deletion of SLC25A51 reduces p16INK4a levels, lowers circulating insulin and glucose levels, and improves insulin sensitivity; NRF2 is implicated as a transcriptional regulator of SLC25A51 upregulation during senescence.\",\n      \"method\": \"Beta-cell-specific Slc25a51 KO mice, SLC25A51 overexpression with transport-dead mutant control, p16INK4a measurement, glucose/insulin tolerance tests, senescence markers\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — transport-dead mutant control distinguishes transporter activity from other effects; preprint, not yet peer-reviewed\",\n      \"pmids\": [\"40642112\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Adipocyte-specific deletion of Slc25a51 markedly reduces adipose tissue mitochondrial NAD+ levels and impairs mitochondrial respiratory function, fatty acid oxidation capacity, and adiponectin production, leading to age-associated obesity, insulin resistance, and hepatosteatosis; adipocyte-specific overexpression protects against obesity and insulin resistance caused by aging.\",\n      \"method\": \"Adipocyte-specific Slc25a51 KO and OE mouse models, mitochondrial NAD+ quantification, respirometry, fatty acid oxidation assays, adiponectin measurement, metabolic phenotyping\",\n      \"journal\": \"Aging cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — tissue-specific KO and OE with multiple orthogonal metabolic readouts; single lab\",\n      \"pmids\": [\"42015379\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SLC25A51 (MCART1) is the mammalian mitochondrial inner-membrane NAD+ transporter that selectively imports oxidized NAD+ into the mitochondrial matrix; it operates via a cardiolipin-assisted, ligand-induced mechanism in which NAD+ engages a negatively charged pore patch and residue E132 to weaken a salt-bridge gate, enabling transport; by controlling mitochondrial NAD+ availability, SLC25A51 sustains TCA cycle flux, ETC complex I activity, and oxidative phosphorylation, and is required for NAD+-dependent sirtuin (SIRT3) deacetylase activity in mitochondria, with its protein stability regulated by OGDHC-mediated K264 succinylation and its transcription regulated by BACH1.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SLC25A51 (MCART1) is the mammalian mitochondrial inner-membrane carrier that selectively imports oxidized NAD+ into the mitochondrial matrix, establishing the supply of NAD+ that drives mitochondrial redox metabolism [#0, #1]. Its identity as a NAD+ transporter rests on convergent evidence: loss of SLC25A51 selectively depletes mitochondrial (not whole-cell) NAD+ and abolishes NAD+ uptake into isolated mitochondria, while overexpression of SLC25A51 or its paralogue SLC25A52 restores uptake and rescues yeast mitochondria lacking endogenous NAD+ transporters [#0]. By controlling matrix NAD+ availability, SLC25A51 sustains TCA cycle flux, ETC complex I activity, and mitochondrial respiration [#1], and AML cells upregulate it to maintain oxidative metabolism from multiple fuels [#7]. Mechanistically, transport is cardiolipin-assisted and ligand-led: cardiolipin engages three exterior sites required for activity, an electrostatic interaction between the nicotinamide ring and a negatively charged pore patch governs selectivity for NAD+ over NADH, and interior residue E132 weakens a salt-bridge matrix gate to initiate transport [#3]. Downstream, matrix NAD+ delivered by SLC25A51 is required for SIRT3 deacetylase activity, so its loss elevates mitochondrial protein acetylation, impairing SIRT3 targets including IDH2, ACADL, and the proline-biosynthetic enzyme P5CS [#4, #5]. Loss of mitochondrial import also redistributes NAD+ to the nucleus and cytoplasm, increasing PARP1-mediated ADP-ribosylation and single-strand break repair and reducing PARP-inhibitor sensitivity [#6]. SLC25A51 abundance is set transcriptionally by repression from BACH1 [#8] and post-translationally by OGDHC-mediated K264 succinylation that stabilizes the protein [#9], and its activity influences cellular senescence and systemic metabolism in beta cells and adipose tissue [#11].\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"Established the long-sought identity of the mammalian mitochondrial NAD+ transporter, resolving how the matrix obtains NAD+ when no eukaryotic carrier had been defined.\",\n      \"evidence\": \"Mitochondrial NAD+ quantification, in vitro NAD+ uptake into isolated mitochondria, and functional complementation in yeast lacking endogenous NAD+ transporters in KO/OE cells\",\n      \"pmids\": [\"32906142\", \"33087354\", \"33262325\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of transport not resolved at this stage\", \"Did not define transport mechanism or selectivity determinants\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Connected the transport function to downstream bioenergetics, showing that mitochondrial NAD+ import is rate-limiting for oxidative metabolism rather than a passive housekeeping process.\",\n      \"evidence\": \"TCA flux analysis, Seahorse respirometry, ETC complex I activity assays, and in vitro uptake in MCART1-null cells\",\n      \"pmids\": [\"33087354\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not address how transporter abundance is regulated\", \"Tissue- and disease-specific roles not examined\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined the molecular transport mechanism, explaining how the carrier achieves NAD+ selectivity and gates substrate passage across the inner membrane.\",\n      \"evidence\": \"Molecular dynamics simulations with lipid bilayer reconstitution plus site-directed mutagenesis of cardiolipin sites and gating residues with functional transport assays\",\n      \"pmids\": [\"37575034\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No experimental high-resolution structure reported\", \"MD-derived gating model not independently replicated\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Linked SLC25A51-supplied matrix NAD+ to SIRT3 function, establishing a regulatory consequence of import on mitochondrial protein acetylation in liver.\",\n      \"evidence\": \"shRNA knockdown in hepatocytes and mouse liver with mitochondrial NAD+ quantification, SIRT3-target acetylation (IDH2, ACADL) westerns, and OCR measurement\",\n      \"pmids\": [\"35932995\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Direct demonstration that acetylation changes are SIRT3-dependent in vivo not fully resolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Extended the SIRT3 axis to a specific metabolic output and identified a pharmacological inhibitor, showing import loss impairs proline biosynthesis via P5CS hyperacetylation.\",\n      \"evidence\": \"KO cell lines with P5CS enzymatic activity assay, acetylation and proline measurements, and fludarabine phosphate drug-binding assays\",\n      \"pmids\": [\"37419986\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Specificity of fludarabine phosphate for SLC25A51 versus other targets not fully delineated\", \"Single lab\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Revealed a cross-compartment consequence of transport loss, showing mitochondrial NAD+ import competes with nuclear NAD+-dependent PARP1 signaling and DNA repair.\",\n      \"evidence\": \"KO cells with subcellular NAD+ measurement, ADP-ribosylation and single-strand break repair assays, PARP1 chromatin retention, and PARP-inhibitor sensitivity in breast cancer cells\",\n      \"pmids\": [\"37587695\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of NAD+ redistribution between compartments not fully defined\", \"Single lab\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Demonstrated a cancer dependency, showing AML cells upregulate SLC25A51 to sustain oxidative metabolism from multiple fuels.\",\n      \"evidence\": \"Isotope-tracing metabolic flux analysis with shRNA depletion, orthotopic xenografts, and combination treatment with 5-azacytidine in vivo\",\n      \"pmids\": [\"38354740\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Generalizability beyond AML not established\", \"Single lab\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identified transcriptional control of the transporter, placing SLC25A51 under repression by BACH1 with functional consequences for endothelial proliferation.\",\n      \"evidence\": \"Dual-luciferase reporter, EMSA, BACH1-KO mice, shRNA rescue, and ETC complex activity assays in HUVECs\",\n      \"pmids\": [\"40312332\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Whether BACH1 regulation operates in other tissues unknown\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Defined post-translational control of transporter stability, identifying OGDHC-mediated K264 succinylation as a stabilizing modification exploited for synthetic lethality in KRAS-mutant AML.\",\n      \"evidence\": \"MS identification of K264 succinylation, mutagenesis, compound 615 treatment, stability and mitochondrial NAD+ assays, and in vivo AML models\",\n      \"pmids\": [\"41616775\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab, abstract-level description\", \"Selectivity of compound 615 between SLC25A51 and SDH not fully characterized\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Established systemic physiological roles, showing SLC25A51 controls mitochondrial NAD+ and oxidative function in adipose tissue and beta cells with consequences for aging metabolism.\",\n      \"evidence\": \"Tissue-specific KO and OE mouse models with mitochondrial NAD+ quantification, respirometry, fatty acid oxidation, adiponectin, and senescence/metabolic phenotyping\",\n      \"pmids\": [\"42015379\", \"40642112\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Beta-cell senescence findings remain a preprint not yet peer-reviewed\", \"Mechanism linking NRF2 to SLC25A51 in senescence not fully resolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"An experimental high-resolution structure of SLC25A51 in substrate-bound and gated states is still needed to confirm the MD-derived transport and selectivity model.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No experimental structure in the corpus\", \"Conformational cycle of the carrier inferred only from simulation\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005215\", \"supporting_discovery_ids\": [0, 1, 3, 7]},\n      {\"term_id\": \"GO:0140104\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [1, 7]},\n      {\"term_id\": \"R-HSA-382551\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}