{"gene":"SLC25A39","run_date":"2026-04-28T20:42:07","timeline":{"discoveries":[{"year":2021,"finding":"SLC25A39 is a mitochondrial membrane carrier required for glutathione (GSH) import into mitochondria; its loss reduces mitochondrial GSH without affecting cellular GSH levels, and cells lacking both SLC25A39 and its paralog SLC25A40 show defects in iron-sulfur cluster protein activity and stability. Mitochondrial GSH import via SLC25A39 is necessary for cell proliferation in vitro and red blood cell development in mice. GSH availability negatively regulates SLC25A39 protein abundance, coupling redox homeostasis to mitochondrial GSH import.","method":"Organellar proteomics, metabolomics, genetic knockout (SLC25A39 and SLC25A39/SLC25A40 double KO), heterologous expression of bacterial GshF in mitochondria, mouse genetic models","journal":"Nature","confidence":"High","confidence_rationale":"Tier 1-2 — multiple orthogonal methods (metabolomics, proteomics, genetic rescue with GshF, mouse models), highly cited foundational study","pmids":["34707288"],"is_preprint":false},{"year":2022,"finding":"SLC25A39 is critical for mitochondrial GSH import as established by mitochondrial metabolite profiling, organelle transport assays, and structure-guided mutagenesis. A genetic buffering interaction exists between SLC25A39-mediated glutathione homeostasis and SLC25A37-mediated mitochondrial iron uptake, and both operate jointly to support mitochondrial OXPHOS.","method":"Dual CRISPR pooled screening in four metabolic states, mitochondrial metabolite profiling, organelle transport assays, structure-guided mutagenesis","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1-2 — multiple orthogonal methods including transport assays and mutagenesis, replicated core finding of GSH import","pmids":["35513392"],"is_preprint":false},{"year":2023,"finding":"SLC25A39 is a short-lived protein degraded by the mitochondrial m-AAA protease AFG3L2 through its matrix loop 1. SLC25A39 senses mitochondrial iron-sulfur cluster status via four matrix cysteine residues, which inhibits its degradation by AFG3L2, thereby coupling mitochondrial iron homeostasis to glutathione import.","method":"Co-immunoprecipitation mass spectrometry, CRISPR knockout in mammalian cells, mutagenesis of cysteine residues, protein stability assays","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1-2 — reciprocal Co-IP/MS, CRISPR KO, mutagenesis; multiple orthogonal methods in single study","pmids":["38157846"],"is_preprint":false},{"year":2001,"finding":"FLAG-tagged CGI-69 (the human protein later identified as SLC25A39) localizes to mitochondria of MCF7 cells when overexpressed, consistent with its classification as a mitochondrial carrier protein.","method":"Transfection of FLAG-tagged CGI-69 with mitochondrial localization assay by fluorescence microscopy","journal":"The Biochemical journal","confidence":"Medium","confidence_rationale":"Tier 3 — direct localization experiment but limited functional follow-up for this protein specifically","pmids":["11139402"],"is_preprint":false},{"year":2024,"finding":"GSH inhibits cuproptosis by chelating copper, and increased GSH is transported into mitochondria via SLC25A39 downstream of the NFE2L2 (NRF2) transcription factor; genetic inhibition of the NFE2L2-GSH-SLC25A39 pathway enhances cuproptosis-mediated tumor suppression in cell culture and in mouse tumor models.","method":"Genetic inhibition (knockdown/knockout) of NFE2L2, GCLM, GCLC, and SLC25A39; cell culture and xenograft mouse models; biochemical copper chelation assays","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2-3 — genetic epistasis in cell and mouse models; single lab with multiple perturbations","pmids":["39609608"],"is_preprint":false},{"year":2025,"finding":"FGF21 enhances mitochondrial GSH uptake by targeting SLC25A39, not by affecting SLC25A39 transcription but by inhibiting AFG3L2-mediated protein degradation, thereby stabilizing SLC25A39 protein. In neuron-specific Slc25a39 knockout mice, FGF21 failed to exert neuroprotective effects after traumatic brain injury, placing SLC25A39 downstream of FGF21 signaling.","method":"Western blot, RT-PCR, FGF21 knockout and recombinant FGF21 rescue, neuron-specific Slc25a39 knockout mice, behavioral assays, transmission electron microscopy","journal":"Journal of translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 — genetic epistasis via neuron-specific KO, FGF21 KO rescue, and protease inhibition mechanism; single lab","pmids":["41039428"],"is_preprint":false},{"year":2025,"finding":"Cytoplasmic CRABP2 interacts with AFG3L2, and the AFG3L2-SLC25A39 axis increases mitochondrial glutathione stability to promote CRC cell proliferation independent of nuclear RB1 pathway.","method":"Co-immunoprecipitation, conditional knockout mouse model (Crabp2ΔIEC), subcutaneous tumorigenesis assay, in vitro functional assays","journal":"Advanced science","confidence":"Medium","confidence_rationale":"Tier 2-3 — Co-IP and genetic mouse model; pathway placement of SLC25A39 downstream of AFG3L2/CRABP2 axis","pmids":["40305785"],"is_preprint":false},{"year":2025,"finding":"DLAT directly binds to SLC25A39 and enhances its protein stability independent of intracellular GSH levels, maintaining mitochondrial GSH import. Knockdown of either DLAT or SLC25A39 disrupts mitochondrial GSH transport and sensitizes cells to ferroptosis.","method":"Co-immunoprecipitation, protein stability assays, GSH/ROS assays, siRNA knockdown of DLAT and SLC25A39, in vitro and in vivo tumor models","journal":"Free radical biology & medicine","confidence":"Medium","confidence_rationale":"Tier 2-3 — direct binding confirmed by Co-IP, functional rescue experiments; single lab","pmids":["42009144"],"is_preprint":false},{"year":2026,"finding":"SLC25A39 directly binds PRDX1 (peroxiredoxin 1) as identified by mass spectrometry and co-immunoprecipitation with co-localization by immunofluorescence. SLC25A39 stabilizes PRDX1 to suppress ROS-induced necroptosis (RIPK1/RIPK3/p-MLKL pathway), and PRDX1 overexpression rescues proliferative/invasive phenotypes in SLC25A39-deficient HCC cells.","method":"Mass spectrometry, co-immunoprecipitation, immunofluorescence, ROS/GSH/MDA assays, RNA-seq, pharmacological inhibition, PRDX1 rescue experiments","journal":"International immunopharmacology","confidence":"Medium","confidence_rationale":"Tier 2-3 — direct binding partner identified by MS and Co-IP; functional rescue of KD phenotype by PRDX1 OE; single lab","pmids":["41558298"],"is_preprint":false},{"year":2025,"finding":"In myoblasts, a reciprocal Slc25a39-Nrf2 redox axis couples glutamine availability to mitochondrial remodeling and myogenic commitment. Nrf2-dependent upregulation of Slc25a39 drives Poised Metabolic Arrest (PMA) under glutamine limitation; silencing Slc25a39 forces premature exit from PMA, compromising differentiation. Both loss and overexpression of Slc25a39 impair myoblast differentiation in vitro and disrupt muscle regeneration in vivo.","method":"Transcriptomic profiling, Slc25a39 siRNA knockdown, Slc25a39 overexpression, glutamine withdrawal experiments, in vivo muscle regeneration model, mitochondrial functional assays","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 — multiple orthogonal methods (transcriptomics, genetic KD/OE, in vivo model); preprint, not yet peer-reviewed","pmids":["bio_10.1101_2025.10.02.680066"],"is_preprint":true}],"current_model":"SLC25A39 is a mitochondrial inner membrane carrier that imports glutathione (GSH) from the cytosol into the mitochondrial matrix; its protein abundance is post-translationally controlled by dual regulation — degradation by the m-AAA protease AFG3L2 through matrix loop 1, and stabilization when SLC25A39 senses mitochondrial iron-sulfur cluster status via four matrix cysteine residues — thereby coupling mitochondrial iron homeostasis and redox state to the regulation of mitochondrial GSH levels, which are required for iron-sulfur cluster protein function, OXPHOS, cell proliferation, and red blood cell development."},"narrative":{"teleology":[{"year":2001,"claim":"Establishing where SLC25A39 resides: before any function was known, demonstrating that the CGI-69 gene product localizes to mitochondria placed it within the mitochondrial carrier family and framed subsequent transport hypotheses.","evidence":"FLAG-tagged CGI-69 overexpression with fluorescence microscopy in MCF7 cells","pmids":["11139402"],"confidence":"Medium","gaps":["No transport substrate identified","Localization based on overexpression only, not endogenous protein","No functional characterization performed"]},{"year":2021,"claim":"Identifying the transported substrate: organellar metabolomics and genetic rescue revealed that SLC25A39 is the long-sought mitochondrial GSH importer, resolving how GSH enters the matrix and showing this is essential for iron-sulfur cluster protein function, proliferation, and erythropoiesis.","evidence":"SLC25A39 KO and SLC25A39/SLC25A40 double KO in cell lines with mitochondrial metabolomics; bacterial GshF rescue; mouse genetic models","pmids":["34707288"],"confidence":"High","gaps":["Direct reconstitution of GSH transport by purified SLC25A39 not shown","Counter-substrate for the exchange cycle not identified","Structural basis for GSH recognition unknown"]},{"year":2022,"claim":"Confirming transport function and revealing genetic buffering: organelle transport assays and structure-guided mutagenesis independently validated SLC25A39 as a mitochondrial GSH transporter and uncovered a functional interaction with the iron importer SLC25A37, linking GSH and iron uptake to joint OXPHOS support.","evidence":"Dual CRISPR screens in four metabolic states, mitochondrial metabolite profiling, organelle transport assays, mutagenesis","pmids":["35513392"],"confidence":"High","gaps":["Molecular basis of the SLC25A39–SLC25A37 genetic interaction unresolved","No reconstituted liposomal transport with purified protein","Selectivity for GSH versus GSSG or other thiol substrates not rigorously defined"]},{"year":2023,"claim":"Decoding the degradation switch: identifying AFG3L2 as the protease that degrades SLC25A39 via matrix loop 1, and showing that four matrix cysteines sense iron-sulfur cluster status to block this degradation, revealed how cells couple iron homeostasis to mitochondrial GSH supply at the post-translational level.","evidence":"Co-IP/MS, CRISPR KO of AFG3L2, cysteine-to-alanine mutagenesis, protein stability assays in mammalian cells","pmids":["38157846"],"confidence":"High","gaps":["Whether cysteines sense Fe-S clusters directly or via a cofactor/adaptor is unresolved","Structural model of AFG3L2 recognition of matrix loop 1 lacking","Relative contributions of GSH-dependent versus Fe-S-dependent regulation not quantified"]},{"year":2024,"claim":"Extending SLC25A39 function to copper-mediated cell death: placing SLC25A39 downstream of the NRF2-GSH axis showed that mitochondrial GSH import protects cells from cuproptosis by chelating copper, and that blocking this axis enhances cuproptosis-mediated tumor suppression.","evidence":"Genetic KD/KO of NFE2L2, GCLM, GCLC, SLC25A39 in cell lines and xenograft mouse models; copper chelation assays","pmids":["39609608"],"confidence":"Medium","gaps":["Direct copper binding by mitochondrial GSH not biochemically demonstrated","Whether SLC25A39 regulation changes under copper stress is unknown","Single-laboratory finding"]},{"year":2025,"claim":"Identifying additional stability regulators and downstream effectors: FGF21 stabilizes SLC25A39 by inhibiting AFG3L2-mediated degradation for neuroprotection; DLAT directly binds and stabilizes SLC25A39 independently of GSH to maintain mitochondrial GSH and resist ferroptosis; CRABP2 modulates the AFG3L2-SLC25A39 axis in colorectal cancer; and SLC25A39 stabilizes PRDX1 to suppress necroptosis in hepatocellular carcinoma.","evidence":"Neuron-specific Slc25a39 KO mice with FGF21 rescue; Co-IP identifying DLAT and PRDX1 as direct binding partners; Crabp2 conditional KO mouse model; protein stability and cell death assays","pmids":["41039428","42009144","40305785","41558298"],"confidence":"Medium","gaps":["DLAT and PRDX1 interactions each reported by single labs without independent replication","Whether DLAT binding and Fe-S cluster sensing act through the same or distinct stabilization mechanisms is unclear","How SLC25A39 stabilizes PRDX1 mechanistically is unknown"]},{"year":null,"claim":"Key open questions include the atomic structure of SLC25A39, direct reconstitution of GSH transport in proteoliposomes, the identity of the counter-substrate, and the precise mechanism by which matrix cysteines sense iron-sulfur cluster occupancy.","evidence":"","pmids":[],"confidence":"High","gaps":["No high-resolution structure of SLC25A39 available","Reconstituted transport with purified protein not demonstrated","Counter-substrate identity unknown","Molecular mechanism of cysteine-mediated Fe-S cluster sensing unresolved"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005215","term_label":"transporter activity","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[0,1,3]}],"pathway":[{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[0,1]}],"complexes":[],"partners":["SLC25A40","AFG3L2","DLAT","PRDX1","CRABP2","SLC25A37"],"other_free_text":[]},"mechanistic_narrative":"SLC25A39 is a mitochondrial inner membrane carrier that imports glutathione (GSH) from the cytosol into the mitochondrial matrix, thereby sustaining iron-sulfur cluster biogenesis, oxidative phosphorylation, and cellular redox defense. Loss of SLC25A39 selectively depletes mitochondrial GSH without affecting cytosolic pools, and combined deletion with its paralog SLC25A40 impairs iron-sulfur cluster protein activity, cell proliferation, and red blood cell development in mice [PMID:34707288, PMID:35513392]. SLC25A39 is a short-lived protein whose abundance is controlled by degradation through the m-AAA protease AFG3L2 via matrix loop 1, with stabilization occurring when four matrix cysteine residues sense iron-sulfur cluster status, directly coupling mitochondrial iron homeostasis to GSH import capacity [PMID:38157846]. Additional stabilizing inputs include DLAT binding independent of GSH levels and FGF21 signaling that inhibits AFG3L2-mediated turnover, linking SLC25A39 regulation to metabolic and neuroprotective pathways [PMID:42009144, PMID:41039428]."},"prefetch_data":{"uniprot":{"accession":"Q9BZJ4","full_name":"Mitochondrial glutathione transporter SLC25A39","aliases":["Solute carrier family 25 member 39"],"length_aa":359,"mass_kda":39.2,"function":"Mitochondrial transporter required for glutathione import into mitochondria (PubMed:34707288, PubMed:35513392, PubMed:37917749, PubMed:38157846). Glutathione, which plays key roles in oxidative metabolism, is produced exclusively in the cytosol and is imported in many organelles (PubMed:34707288). Mitochondrial glutathione is required for the activity and stability of proteins containing iron-sulfur clusters, as well as erythropoiesis (PubMed:34707288)","subcellular_location":"Mitochondrion inner membrane","url":"https://www.uniprot.org/uniprotkb/Q9BZJ4/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SLC25A39","classification":"Not Classified","n_dependent_lines":11,"n_total_lines":1208,"dependency_fraction":0.009105960264900662},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/SLC25A39","total_profiled":1310},"omim":[{"mim_id":"610820","title":"SOLUTE CARRIER FAMILY 25, MEMBER 39; SLC25A39","url":"https://www.omim.org/entry/610820"},{"mim_id":"138945","title":"GRANULIN PRECURSOR; GRN","url":"https://www.omim.org/entry/138945"}],"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/SLC25A39"},"hgnc":{"alias_symbol":["FLJ22407","CGI-69"],"prev_symbol":[]},"alphafold":{"accession":"Q9BZJ4","domains":[{"cath_id":"1.50.40.10","chopping":"12-37_108-359","consensus_level":"medium","plddt":81.3991,"start":12,"end":359}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BZJ4","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BZJ4-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BZJ4-F1-predicted_aligned_error_v6.png","plddt_mean":73.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SLC25A39","jax_strain_url":"https://www.jax.org/strain/search?query=SLC25A39"},"sequence":{"accession":"Q9BZJ4","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BZJ4.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BZJ4/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BZJ4"}},"corpus_meta":[{"pmid":"34707288","id":"PMC_34707288","title":"SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells.","date":"2021","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/34707288","citation_count":196,"is_preprint":false},{"pmid":"35513392","id":"PMC_35513392","title":"Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS.","date":"2022","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/35513392","citation_count":83,"is_preprint":false},{"pmid":"38157846","id":"PMC_38157846","title":"Dual regulation of SLC25A39 by AFG3L2 and iron controls mitochondrial glutathione homeostasis.","date":"2023","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/38157846","citation_count":35,"is_preprint":false},{"pmid":"11139402","id":"PMC_11139402","title":"Overexpression of the human 2-oxoglutarate carrier lowers mitochondrial membrane potential in HEK-293 cells: contrast with the unique cold-induced mitochondrial carrier CGI-69.","date":"2001","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/11139402","citation_count":32,"is_preprint":false},{"pmid":"39609608","id":"PMC_39609608","title":"NFE2L2 and SLC25A39 drive cuproptosis resistance through GSH metabolism.","date":"2024","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/39609608","citation_count":28,"is_preprint":false},{"pmid":"35955707","id":"PMC_35955707","title":"Slc25a39 and Slc25a40 Expression in Mice with Bile Duct Ligation or Lipopolysaccharide Treatment.","date":"2022","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/35955707","citation_count":11,"is_preprint":false},{"pmid":"38364779","id":"PMC_38364779","title":"SLC25A39 links mitochondrial GSH sensing with iron metabolism.","date":"2024","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/38364779","citation_count":10,"is_preprint":false},{"pmid":"39308681","id":"PMC_39308681","title":"Up-regulated SLC25A39 promotes cell growth and metastasis via regulating ROS production in colorectal cancer.","date":"2024","source":"Journal of Cancer","url":"https://pubmed.ncbi.nlm.nih.gov/39308681","citation_count":6,"is_preprint":false},{"pmid":"33963205","id":"PMC_33963205","title":"Germinal GLT8D1, GATAD2A and SLC25A39 mutations in a patient with a glomangiopericytal tumor and five different sarcomas over a 10-year period.","date":"2021","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/33963205","citation_count":5,"is_preprint":false},{"pmid":"40305785","id":"PMC_40305785","title":"Dual Role of CRABP2 in Colorectal Cancer: Oncogenesis via Nuclear RB1 and Cytoplasmic AFG3L2/SLC25A39 Axis, While Limiting Liver Metastasis through Cytoplasmic AFG3L2/PINK1/Parkin-Mediated Mitophagy.","date":"2025","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/40305785","citation_count":3,"is_preprint":false},{"pmid":"41039428","id":"PMC_41039428","title":"FGF21 maintains redox homeostasis and promotes neuronal survival after traumatic brain injury by targeting SLC25A39-mediated mitochondrial GSH transport.","date":"2025","source":"Journal of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/41039428","citation_count":2,"is_preprint":false},{"pmid":"40993178","id":"PMC_40993178","title":"SLC25A39 overexpression exacerbates lung adenocarcinoma progression and is negatively regulated by AFG3L2.","date":"2025","source":"NPJ precision oncology","url":"https://pubmed.ncbi.nlm.nih.gov/40993178","citation_count":1,"is_preprint":false},{"pmid":"41093994","id":"PMC_41093994","title":"SLC25A39 regulates Hedgehog signaling to promote tumor progression and sorafenib resistance in hepatocellular carcinoma.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/41093994","citation_count":1,"is_preprint":false},{"pmid":"41430562","id":"PMC_41430562","title":"SLC25A39 identified as a key regulator of hepatocellular carcinoma progression through the mitochondrial ROS-cytochrome c-caspase signaling axis.","date":"2025","source":"Cellular & molecular biology letters","url":"https://pubmed.ncbi.nlm.nih.gov/41430562","citation_count":0,"is_preprint":false},{"pmid":"42009144","id":"PMC_42009144","title":"DLAT sustains redox homeostasis and prevent colorectal cancer from ferroptosis by regulating SLC25A39-mediated mitochondrial glutathione transport.","date":"2026","source":"Free radical biology & medicine","url":"https://pubmed.ncbi.nlm.nih.gov/42009144","citation_count":0,"is_preprint":false},{"pmid":"41558298","id":"PMC_41558298","title":"SLC25A39 binds and modulates PRDX1 to suppress ROS-induced necroptosis in hepatocellular carcinoma.","date":"2026","source":"International immunopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/41558298","citation_count":0,"is_preprint":false},{"pmid":"41495816","id":"PMC_41495816","title":"SLC25A39 facilitates Sorafenib resistance in hepatocellular carcinoma by inhibiting mitochondrial oxidative stress-induced ferroptosis.","date":"2026","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/41495816","citation_count":0,"is_preprint":false},{"pmid":"40587910","id":"PMC_40587910","title":"The screening and validation of lnc-SLC25A39 and lnc-LINC00279-202 for distinguishing tissue origins of peripheral blood and semen samples by RT-qPCR.","date":"2025","source":"Legal medicine (Tokyo, Japan)","url":"https://pubmed.ncbi.nlm.nih.gov/40587910","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.10.02.680066","title":"Glutamine-Dependent Slc25a39–Nrf2 Axis Couples Mitochondrial Dynamics with Metabolic Reprogramming to Establish Myogenic Commitment","date":"2025-10-04","source":"bioRxiv","url":"https://doi.org/10.1101/2025.10.02.680066","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10596,"output_tokens":2674,"usd":0.035949},"stage2":{"model":"claude-opus-4-6","input_tokens":5993,"output_tokens":4235,"usd":0.20376},"total_usd":0.239709,"stage1_batch_id":"msgbatch_011rkcQdVV1RaFq9XhcG6df6","stage2_batch_id":"msgbatch_01RzgrJafdF4EWHhj5mNi6dh","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2021,\n      \"finding\": \"SLC25A39 is a mitochondrial membrane carrier required for glutathione (GSH) import into mitochondria; its loss reduces mitochondrial GSH without affecting cellular GSH levels, and cells lacking both SLC25A39 and its paralog SLC25A40 show defects in iron-sulfur cluster protein activity and stability. Mitochondrial GSH import via SLC25A39 is necessary for cell proliferation in vitro and red blood cell development in mice. GSH availability negatively regulates SLC25A39 protein abundance, coupling redox homeostasis to mitochondrial GSH import.\",\n      \"method\": \"Organellar proteomics, metabolomics, genetic knockout (SLC25A39 and SLC25A39/SLC25A40 double KO), heterologous expression of bacterial GshF in mitochondria, mouse genetic models\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal methods (metabolomics, proteomics, genetic rescue with GshF, mouse models), highly cited foundational study\",\n      \"pmids\": [\"34707288\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"SLC25A39 is critical for mitochondrial GSH import as established by mitochondrial metabolite profiling, organelle transport assays, and structure-guided mutagenesis. A genetic buffering interaction exists between SLC25A39-mediated glutathione homeostasis and SLC25A37-mediated mitochondrial iron uptake, and both operate jointly to support mitochondrial OXPHOS.\",\n      \"method\": \"Dual CRISPR pooled screening in four metabolic states, mitochondrial metabolite profiling, organelle transport assays, structure-guided mutagenesis\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal methods including transport assays and mutagenesis, replicated core finding of GSH import\",\n      \"pmids\": [\"35513392\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SLC25A39 is a short-lived protein degraded by the mitochondrial m-AAA protease AFG3L2 through its matrix loop 1. SLC25A39 senses mitochondrial iron-sulfur cluster status via four matrix cysteine residues, which inhibits its degradation by AFG3L2, thereby coupling mitochondrial iron homeostasis to glutathione import.\",\n      \"method\": \"Co-immunoprecipitation mass spectrometry, CRISPR knockout in mammalian cells, mutagenesis of cysteine residues, protein stability assays\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — reciprocal Co-IP/MS, CRISPR KO, mutagenesis; multiple orthogonal methods in single study\",\n      \"pmids\": [\"38157846\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"FLAG-tagged CGI-69 (the human protein later identified as SLC25A39) localizes to mitochondria of MCF7 cells when overexpressed, consistent with its classification as a mitochondrial carrier protein.\",\n      \"method\": \"Transfection of FLAG-tagged CGI-69 with mitochondrial localization assay by fluorescence microscopy\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — direct localization experiment but limited functional follow-up for this protein specifically\",\n      \"pmids\": [\"11139402\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"GSH inhibits cuproptosis by chelating copper, and increased GSH is transported into mitochondria via SLC25A39 downstream of the NFE2L2 (NRF2) transcription factor; genetic inhibition of the NFE2L2-GSH-SLC25A39 pathway enhances cuproptosis-mediated tumor suppression in cell culture and in mouse tumor models.\",\n      \"method\": \"Genetic inhibition (knockdown/knockout) of NFE2L2, GCLM, GCLC, and SLC25A39; cell culture and xenograft mouse models; biochemical copper chelation assays\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — genetic epistasis in cell and mouse models; single lab with multiple perturbations\",\n      \"pmids\": [\"39609608\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"FGF21 enhances mitochondrial GSH uptake by targeting SLC25A39, not by affecting SLC25A39 transcription but by inhibiting AFG3L2-mediated protein degradation, thereby stabilizing SLC25A39 protein. In neuron-specific Slc25a39 knockout mice, FGF21 failed to exert neuroprotective effects after traumatic brain injury, placing SLC25A39 downstream of FGF21 signaling.\",\n      \"method\": \"Western blot, RT-PCR, FGF21 knockout and recombinant FGF21 rescue, neuron-specific Slc25a39 knockout mice, behavioral assays, transmission electron microscopy\",\n      \"journal\": \"Journal of translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis via neuron-specific KO, FGF21 KO rescue, and protease inhibition mechanism; single lab\",\n      \"pmids\": [\"41039428\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Cytoplasmic CRABP2 interacts with AFG3L2, and the AFG3L2-SLC25A39 axis increases mitochondrial glutathione stability to promote CRC cell proliferation independent of nuclear RB1 pathway.\",\n      \"method\": \"Co-immunoprecipitation, conditional knockout mouse model (Crabp2ΔIEC), subcutaneous tumorigenesis assay, in vitro functional assays\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — Co-IP and genetic mouse model; pathway placement of SLC25A39 downstream of AFG3L2/CRABP2 axis\",\n      \"pmids\": [\"40305785\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DLAT directly binds to SLC25A39 and enhances its protein stability independent of intracellular GSH levels, maintaining mitochondrial GSH import. Knockdown of either DLAT or SLC25A39 disrupts mitochondrial GSH transport and sensitizes cells to ferroptosis.\",\n      \"method\": \"Co-immunoprecipitation, protein stability assays, GSH/ROS assays, siRNA knockdown of DLAT and SLC25A39, in vitro and in vivo tumor models\",\n      \"journal\": \"Free radical biology & medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — direct binding confirmed by Co-IP, functional rescue experiments; single lab\",\n      \"pmids\": [\"42009144\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"SLC25A39 directly binds PRDX1 (peroxiredoxin 1) as identified by mass spectrometry and co-immunoprecipitation with co-localization by immunofluorescence. SLC25A39 stabilizes PRDX1 to suppress ROS-induced necroptosis (RIPK1/RIPK3/p-MLKL pathway), and PRDX1 overexpression rescues proliferative/invasive phenotypes in SLC25A39-deficient HCC cells.\",\n      \"method\": \"Mass spectrometry, co-immunoprecipitation, immunofluorescence, ROS/GSH/MDA assays, RNA-seq, pharmacological inhibition, PRDX1 rescue experiments\",\n      \"journal\": \"International immunopharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — direct binding partner identified by MS and Co-IP; functional rescue of KD phenotype by PRDX1 OE; single lab\",\n      \"pmids\": [\"41558298\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In myoblasts, a reciprocal Slc25a39-Nrf2 redox axis couples glutamine availability to mitochondrial remodeling and myogenic commitment. Nrf2-dependent upregulation of Slc25a39 drives Poised Metabolic Arrest (PMA) under glutamine limitation; silencing Slc25a39 forces premature exit from PMA, compromising differentiation. Both loss and overexpression of Slc25a39 impair myoblast differentiation in vitro and disrupt muscle regeneration in vivo.\",\n      \"method\": \"Transcriptomic profiling, Slc25a39 siRNA knockdown, Slc25a39 overexpression, glutamine withdrawal experiments, in vivo muscle regeneration model, mitochondrial functional assays\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (transcriptomics, genetic KD/OE, in vivo model); preprint, not yet peer-reviewed\",\n      \"pmids\": [\"bio_10.1101_2025.10.02.680066\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"SLC25A39 is a mitochondrial inner membrane carrier that imports glutathione (GSH) from the cytosol into the mitochondrial matrix; its protein abundance is post-translationally controlled by dual regulation — degradation by the m-AAA protease AFG3L2 through matrix loop 1, and stabilization when SLC25A39 senses mitochondrial iron-sulfur cluster status via four matrix cysteine residues — thereby coupling mitochondrial iron homeostasis and redox state to the regulation of mitochondrial GSH levels, which are required for iron-sulfur cluster protein function, OXPHOS, cell proliferation, and red blood cell development.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"SLC25A39 is a mitochondrial inner membrane carrier that imports glutathione (GSH) from the cytosol into the mitochondrial matrix, thereby sustaining iron-sulfur cluster biogenesis, oxidative phosphorylation, and cellular redox defense. Loss of SLC25A39 selectively depletes mitochondrial GSH without affecting cytosolic pools, and combined deletion with its paralog SLC25A40 impairs iron-sulfur cluster protein activity, cell proliferation, and red blood cell development in mice [PMID:34707288, PMID:35513392]. SLC25A39 is a short-lived protein whose abundance is controlled by degradation through the m-AAA protease AFG3L2 via matrix loop 1, with stabilization occurring when four matrix cysteine residues sense iron-sulfur cluster status, directly coupling mitochondrial iron homeostasis to GSH import capacity [PMID:38157846]. Additional stabilizing inputs include DLAT binding independent of GSH levels and FGF21 signaling that inhibits AFG3L2-mediated turnover, linking SLC25A39 regulation to metabolic and neuroprotective pathways [PMID:42009144, PMID:41039428].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Establishing where SLC25A39 resides: before any function was known, demonstrating that the CGI-69 gene product localizes to mitochondria placed it within the mitochondrial carrier family and framed subsequent transport hypotheses.\",\n      \"evidence\": \"FLAG-tagged CGI-69 overexpression with fluorescence microscopy in MCF7 cells\",\n      \"pmids\": [\"11139402\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No transport substrate identified\",\n        \"Localization based on overexpression only, not endogenous protein\",\n        \"No functional characterization performed\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identifying the transported substrate: organellar metabolomics and genetic rescue revealed that SLC25A39 is the long-sought mitochondrial GSH importer, resolving how GSH enters the matrix and showing this is essential for iron-sulfur cluster protein function, proliferation, and erythropoiesis.\",\n      \"evidence\": \"SLC25A39 KO and SLC25A39/SLC25A40 double KO in cell lines with mitochondrial metabolomics; bacterial GshF rescue; mouse genetic models\",\n      \"pmids\": [\"34707288\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct reconstitution of GSH transport by purified SLC25A39 not shown\",\n        \"Counter-substrate for the exchange cycle not identified\",\n        \"Structural basis for GSH recognition unknown\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Confirming transport function and revealing genetic buffering: organelle transport assays and structure-guided mutagenesis independently validated SLC25A39 as a mitochondrial GSH transporter and uncovered a functional interaction with the iron importer SLC25A37, linking GSH and iron uptake to joint OXPHOS support.\",\n      \"evidence\": \"Dual CRISPR screens in four metabolic states, mitochondrial metabolite profiling, organelle transport assays, mutagenesis\",\n      \"pmids\": [\"35513392\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular basis of the SLC25A39–SLC25A37 genetic interaction unresolved\",\n        \"No reconstituted liposomal transport with purified protein\",\n        \"Selectivity for GSH versus GSSG or other thiol substrates not rigorously defined\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Decoding the degradation switch: identifying AFG3L2 as the protease that degrades SLC25A39 via matrix loop 1, and showing that four matrix cysteines sense iron-sulfur cluster status to block this degradation, revealed how cells couple iron homeostasis to mitochondrial GSH supply at the post-translational level.\",\n      \"evidence\": \"Co-IP/MS, CRISPR KO of AFG3L2, cysteine-to-alanine mutagenesis, protein stability assays in mammalian cells\",\n      \"pmids\": [\"38157846\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether cysteines sense Fe-S clusters directly or via a cofactor/adaptor is unresolved\",\n        \"Structural model of AFG3L2 recognition of matrix loop 1 lacking\",\n        \"Relative contributions of GSH-dependent versus Fe-S-dependent regulation not quantified\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Extending SLC25A39 function to copper-mediated cell death: placing SLC25A39 downstream of the NRF2-GSH axis showed that mitochondrial GSH import protects cells from cuproptosis by chelating copper, and that blocking this axis enhances cuproptosis-mediated tumor suppression.\",\n      \"evidence\": \"Genetic KD/KO of NFE2L2, GCLM, GCLC, SLC25A39 in cell lines and xenograft mouse models; copper chelation assays\",\n      \"pmids\": [\"39609608\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct copper binding by mitochondrial GSH not biochemically demonstrated\",\n        \"Whether SLC25A39 regulation changes under copper stress is unknown\",\n        \"Single-laboratory finding\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identifying additional stability regulators and downstream effectors: FGF21 stabilizes SLC25A39 by inhibiting AFG3L2-mediated degradation for neuroprotection; DLAT directly binds and stabilizes SLC25A39 independently of GSH to maintain mitochondrial GSH and resist ferroptosis; CRABP2 modulates the AFG3L2-SLC25A39 axis in colorectal cancer; and SLC25A39 stabilizes PRDX1 to suppress necroptosis in hepatocellular carcinoma.\",\n      \"evidence\": \"Neuron-specific Slc25a39 KO mice with FGF21 rescue; Co-IP identifying DLAT and PRDX1 as direct binding partners; Crabp2 conditional KO mouse model; protein stability and cell death assays\",\n      \"pmids\": [\"41039428\", \"42009144\", \"40305785\", \"41558298\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"DLAT and PRDX1 interactions each reported by single labs without independent replication\",\n        \"Whether DLAT binding and Fe-S cluster sensing act through the same or distinct stabilization mechanisms is unclear\",\n        \"How SLC25A39 stabilizes PRDX1 mechanistically is unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key open questions include the atomic structure of SLC25A39, direct reconstitution of GSH transport in proteoliposomes, the identity of the counter-substrate, and the precise mechanism by which matrix cysteines sense iron-sulfur cluster occupancy.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No high-resolution structure of SLC25A39 available\",\n        \"Reconstituted transport with purified protein not demonstrated\",\n        \"Counter-substrate identity unknown\",\n        \"Molecular mechanism of cysteine-mediated Fe-S cluster sensing unresolved\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005215\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0, 1, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"SLC25A40\", \"AFG3L2\", \"DLAT\", \"PRDX1\", \"CRABP2\", \"SLC25A37\"],\n    \"other_free_text\": []\n  }\n}\n```\n\nWait, I need to fix the pathway field - it should use Reactome IDs, not GO IDs. Let me correct:\n\n```json\n{\n  \"mechanistic_narrative\": \"SLC25A39 is a mitochondrial inner membrane carrier that imports glutathione (GSH) from the cytosol into the mitochondrial matrix, thereby sustaining iron-sulfur cluster biogenesis, oxidative phosphorylation, and cellular redox defense. Loss of SLC25A39 selectively depletes mitochondrial GSH without affecting cytosolic pools, and combined deletion with its paralog SLC25A40 impairs iron-sulfur cluster protein activity, cell proliferation, and red blood cell development in mice [PMID:34707288, PMID:35513392]. SLC25A39 is a short-lived protein whose abundance is controlled by degradation through the m-AAA protease AFG3L2 via matrix loop 1, with stabilization occurring when four matrix cysteine residues sense iron-sulfur cluster status, directly coupling mitochondrial iron homeostasis to GSH import capacity [PMID:38157846]. Additional stabilizing inputs include DLAT binding independent of GSH levels and FGF21 signaling that inhibits AFG3L2-mediated turnover, linking SLC25A39 regulation to metabolic and neuroprotective pathways [PMID:42009144, PMID:41039428].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Establishing where SLC25A39 resides: before any function was known, demonstrating that the CGI-69 gene product localizes to mitochondria placed it within the mitochondrial carrier family and framed subsequent transport hypotheses.\",\n      \"evidence\": \"FLAG-tagged CGI-69 overexpression with fluorescence microscopy in MCF7 cells\",\n      \"pmids\": [\"11139402\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No transport substrate identified\",\n        \"Localization based on overexpression only, not endogenous protein\",\n        \"No functional characterization performed\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identifying the transported substrate: organellar metabolomics and genetic rescue revealed that SLC25A39 is the long-sought mitochondrial GSH importer, resolving how GSH enters the matrix and showing this is essential for iron-sulfur cluster protein function, proliferation, and erythropoiesis.\",\n      \"evidence\": \"SLC25A39 KO and SLC25A39/SLC25A40 double KO in cell lines with mitochondrial metabolomics; bacterial GshF rescue; mouse genetic models\",\n      \"pmids\": [\"34707288\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct reconstitution of GSH transport by purified SLC25A39 not shown\",\n        \"Counter-substrate for the exchange cycle not identified\",\n        \"Structural basis for GSH recognition unknown\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Confirming transport function and revealing genetic buffering: organelle transport assays and structure-guided mutagenesis independently validated SLC25A39 as a mitochondrial GSH transporter and uncovered a functional interaction with the iron importer SLC25A37, linking GSH and iron uptake to joint OXPHOS support.\",\n      \"evidence\": \"Dual CRISPR screens in four metabolic states, mitochondrial metabolite profiling, organelle transport assays, mutagenesis\",\n      \"pmids\": [\"35513392\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular basis of the SLC25A39–SLC25A37 genetic interaction unresolved\",\n        \"No reconstituted liposomal transport with purified protein\",\n        \"Selectivity for GSH versus GSSG or other thiol substrates not rigorously defined\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Decoding the degradation switch: identifying AFG3L2 as the protease that degrades SLC25A39 via matrix loop 1, and showing that four matrix cysteines sense iron-sulfur cluster status to block this degradation, revealed how cells couple iron homeostasis to mitochondrial GSH supply at the post-translational level.\",\n      \"evidence\": \"Co-IP/MS, CRISPR KO of AFG3L2, cysteine-to-alanine mutagenesis, protein stability assays in mammalian cells\",\n      \"pmids\": [\"38157846\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether cysteines sense Fe-S clusters directly or via a cofactor/adaptor is unresolved\",\n        \"Structural model of AFG3L2 recognition of matrix loop 1 lacking\",\n        \"Relative contributions of GSH-dependent versus Fe-S-dependent regulation not quantified\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Extending SLC25A39 function to copper-mediated cell death: placing SLC25A39 downstream of the NRF2-GSH axis showed that mitochondrial GSH import protects cells from cuproptosis by chelating copper, and that blocking this axis enhances cuproptosis-mediated tumor suppression.\",\n      \"evidence\": \"Genetic KD/KO of NFE2L2, GCLM, GCLC, SLC25A39 in cell lines and xenograft mouse models; copper chelation assays\",\n      \"pmids\": [\"39609608\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct copper binding by mitochondrial GSH not biochemically demonstrated\",\n        \"Whether SLC25A39 regulation changes under copper stress is unknown\",\n        \"Single-laboratory finding\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identifying additional stability regulators and downstream effectors: FGF21 stabilizes SLC25A39 by inhibiting AFG3L2-mediated degradation for neuroprotection; DLAT directly binds and stabilizes SLC25A39 independently of GSH to maintain mitochondrial GSH and resist ferroptosis; CRABP2 modulates the AFG3L2-SLC25A39 axis in colorectal cancer; and SLC25A39 stabilizes PRDX1 to suppress necroptosis in hepatocellular carcinoma.\",\n      \"evidence\": \"Neuron-specific Slc25a39 KO mice with FGF21 rescue; Co-IP identifying DLAT and PRDX1 as direct binding partners; Crabp2 conditional KO mouse model; protein stability and cell death assays\",\n      \"pmids\": [\"41039428\", \"42009144\", \"40305785\", \"41558298\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"DLAT and PRDX1 interactions each reported by single labs without independent replication\",\n        \"Whether DLAT binding and Fe-S cluster sensing act through the same or distinct stabilization mechanisms is unclear\",\n        \"How SLC25A39 stabilizes PRDX1 mechanistically is unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key open questions include the atomic structure of SLC25A39, direct reconstitution of GSH transport in proteoliposomes, the identity of the counter-substrate, and the precise mechanism by which matrix cysteines sense iron-sulfur cluster occupancy.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No high-resolution structure of SLC25A39 available\",\n        \"Reconstituted transport with purified protein not demonstrated\",\n        \"Counter-substrate identity unknown\",\n        \"Molecular mechanism of cysteine-mediated Fe-S cluster sensing unresolved\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005215\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0, 1, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-382551\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"SLC25A40\", \"AFG3L2\", \"DLAT\", \"PRDX1\", \"CRABP2\", \"SLC25A37\"],\n    \"other_free_text\": []\n  }\n}\n```"}