{"gene":"TMEM11","run_date":"2026-06-10T10:51:55","timeline":{"discoveries":[{"year":2011,"finding":"Drosophila PMI (ortholog of human TMEM11) encodes a mitochondrial inner-membrane protein that regulates mitochondrial morphogenesis. Loss of PMI causes a highly condensed mitochondrial network, indicating a pro-fission or anti-fusion function. Genetic epistasis experiments showed this effect is independent of drp1 (DRP1) and mfn (Mitofusin), establishing a separate pathway for mitochondrial network shaping.","method":"Genetic loss-of-function (PMI mutant cells), epistasis analysis (double mutants with drp1 and mfn), subcellular localization of endogenous protein","journal":"EMBO reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal genetic epistasis with two independent pathways, direct localization, clean loss-of-function phenotype, published in peer-reviewed journal","pmids":["21274005"],"is_preprint":false},{"year":2023,"finding":"TMEM11 forms a complex with BNIP3 and BNIP3L (outer mitochondrial membrane receptor proteins) and co-enriches at sites of mitophagosome formation. Loss of TMEM11 results in hyper-active BNIP3/BNIP3L-mediated mitophagy during both normoxia and hypoxia-mimetic conditions due to an increase in the number of BNIP3/BNIP3L mitophagy sites, supporting a model where TMEM11 spatially restricts mitophagosome formation.","method":"Co-immunoprecipitation (TMEM11 complex with BNIP3/BNIP3L), fluorescence co-localization at mitophagy sites, TMEM11 knockout cells with quantitative mitophagy assays under normoxia and hypoxia-mimetic conditions","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, quantitative mitophagy assays in KO cells, spatial co-localization, two orthogonal methods, peer-reviewed","pmids":["36795401"],"is_preprint":false},{"year":2023,"finding":"TMEM11 directly interacts with METTL1 and enhances m7G methylation of Atf5 mRNA, thereby increasing ATF5 protein expression. Elevated ATF5 promotes transcription of Inca1 (an inhibitor of cyclin-dependent kinase interacting with cyclin A1), which suppresses cardiomyocyte proliferation. TMEM11 deletion enhanced cardiomyocyte proliferation and restored heart function after myocardial injury; TMEM11 overexpression had the opposite effect.","method":"Co-immunoprecipitation (TMEM11-METTL1 interaction), m7G methylation assay of Atf5 mRNA, loss-of-function (TMEM11 deletion) and gain-of-function (TMEM11 overexpression) in cardiomyocytes and mouse hearts, ATF5 reporter/expression analysis, Inca1 transcription assay","journal":"Cell death and differentiation","confidence":"High","confidence_rationale":"Tier 2 / Strong — Co-IP, mRNA methylation assay, in vitro and in vivo loss- and gain-of-function with defined molecular pathway, multiple orthogonal methods in single study","pmids":["37286744"],"is_preprint":false},{"year":2024,"finding":"Both splice variants of zebrafish Tmem11 localize to the outer membrane of mitochondria, as determined by fluorescent tagging in cell culture and biochemical membrane fractionation. This contrasts with the previously reported inner-membrane localization in Drosophila but is consistent with the outer mitochondrial membrane localization reported in mammalian studies.","method":"Fluorescent protein fusion (live imaging in cell culture), biochemical fractionation of mitochondrial membranes","journal":"microPublication biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with two orthogonal methods (imaging + fractionation), single lab, zebrafish ortholog","pmids":["39149412"],"is_preprint":false},{"year":2026,"finding":"TMEM11 inhibits BNIP3-mediated mitophagy and apoptosis in bladder cancer cells, stabilizing mitochondrial function to promote cisplatin resistance. Mechanistically, TMEM11 suppresses BNIP3 expression and impairs mitophagy flux. TMEM11 knockdown reduced tumor growth and sensitized tumors to cisplatin in vivo.","method":"TMEM11 knockdown (siRNA/shRNA), mitophagy flux assays, apoptosis assays, BNIP3 expression analysis, in vivo xenograft with cisplatin treatment, molecular docking (Curcumin as TMEM11 inhibitor)","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined molecular phenotype (BNIP3 suppression, mitophagy flux), in vitro and in vivo validation, single lab","pmids":["41570932"],"is_preprint":false}],"current_model":"TMEM11 is an outer mitochondrial membrane protein that (1) regulates mitochondrial network morphology through a pathway independent of DRP1/Mitofusin fission-fusion machinery, (2) spatially restricts BNIP3/BNIP3L-mediated receptor mitophagy by forming a complex with these receptors and limiting mitophagosome formation sites, (3) interacts with METTL1 to enhance m7G methylation of ATF5 mRNA, promoting ATF5-INCA1 axis-mediated suppression of cardiomyocyte proliferation, and (4) suppresses BNIP3-mediated mitophagy flux to modulate cisplatin resistance in cancer cells."},"narrative":{"mechanistic_narrative":"TMEM11 is a mitochondrial membrane protein that shapes mitochondrial network morphology and constrains receptor-mediated mitophagy [PMID:21274005, PMID:36795401]. It localizes to the outer mitochondrial membrane [PMID:39149412] and regulates network morphology through a pathway genetically separable from the canonical DRP1/Mitofusin fission–fusion machinery, since loss of its Drosophila ortholog PMI produces a condensed network independent of drp1 and mfn [PMID:21274005]. At the mitophagy interface, TMEM11 forms a complex with the outer-membrane receptor proteins BNIP3 and BNIP3L and co-enriches at sites of mitophagosome formation; its loss increases the number of mitophagy sites and hyperactivates BNIP3/BNIP3L-driven mitophagy under both normoxia and hypoxia-mimetic conditions, establishing TMEM11 as a spatial restrictor of mitophagosome nucleation [PMID:36795401]. This BNIP3-suppressing activity has disease relevance: in bladder cancer cells TMEM11 suppresses BNIP3 expression and impairs mitophagy flux to stabilize mitochondria and promote cisplatin resistance [PMID:41570932]. Independent of its membrane role, TMEM11 interacts with the m7G methyltransferase METTL1 to enhance m7G methylation of Atf5 mRNA, raising ATF5 protein and driving an ATF5–INCA1 axis that suppresses cardiomyocyte proliferation [PMID:37286744].","teleology":[{"year":2011,"claim":"Established that TMEM11/PMI controls mitochondrial network shape through a pathway distinct from the known fission–fusion machinery, defining a novel morphogenesis regulator.","evidence":"Genetic loss-of-function and reciprocal epistasis with drp1 and mfn plus endogenous localization in Drosophila","pmids":["21274005"],"confidence":"High","gaps":["Molecular activity producing the condensed-network phenotype not defined","Inner-membrane localization in Drosophila later contradicted by outer-membrane reports in other species","No direct partners identified at this stage"]},{"year":2023,"claim":"Answered how TMEM11 intersects with selective mitophagy, showing it physically partners with BNIP3/BNIP3L and spatially limits where mitophagosomes form.","evidence":"Reciprocal Co-IP, fluorescence co-localization at mitophagy sites, and quantitative mitophagy assays in KO cells under normoxia and hypoxia-mimetic conditions","pmids":["36795401"],"confidence":"High","gaps":["Structural basis for restricting site number unknown","Relationship between morphology role and mitophagy site control not resolved","Whether the BNIP3/BNIP3L complex requires additional subunits unaddressed"]},{"year":2023,"claim":"Revealed an unexpected non-morphology function in which TMEM11 acts through METTL1-dependent mRNA modification to control a proliferation-suppressing transcriptional axis.","evidence":"Co-IP of TMEM11–METTL1, m7G methylation assay of Atf5 mRNA, and in vitro/in vivo loss- and gain-of-function in cardiomyocytes with ATF5–INCA1 readouts","pmids":["37286744"],"confidence":"High","gaps":["How an outer-membrane protein engages a methyltransferase acting on mRNA is mechanistically unexplained","Whether this links to TMEM11's mitochondrial functions unknown","Direct binding interface with METTL1 not mapped"]},{"year":2024,"claim":"Resolved the localization discrepancy by placing TMEM11 at the outer mitochondrial membrane, consistent with its mitophagy-receptor partnerships.","evidence":"Fluorescent fusion live imaging and biochemical membrane fractionation of both zebrafish Tmem11 splice variants","pmids":["39149412"],"confidence":"Medium","gaps":["Single lab, ortholog-based","Topology and membrane-spanning architecture not defined","Does not reconcile with earlier Drosophila inner-membrane report mechanistically"]},{"year":2026,"claim":"Extended the BNIP3-restricting function to a disease context, showing TMEM11 suppresses mitophagy to drive chemoresistance.","evidence":"TMEM11 knockdown with mitophagy flux and apoptosis assays, BNIP3 expression analysis, and in vivo xenograft cisplatin sensitization in bladder cancer","pmids":["41570932"],"confidence":"Medium","gaps":["Single lab","Mechanism of BNIP3 expression suppression versus the earlier spatial-restriction model not reconciled","Curcumin as TMEM11 inhibitor only by docking, not validated biochemically"]},{"year":null,"claim":"The molecular activity that lets TMEM11 both shape mitochondrial networks and gate mitophagosome formation, and how this reconciles with its METTL1/m7G role, remains undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural or enzymatic activity assigned to TMEM11","Unclear whether morphology, mitophagy, and m7G functions share a common mechanism","No reconciliation of suppressing BNIP3 expression versus restricting BNIP3 site number"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[1,4]}],"localization":[{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[0,1,3]}],"pathway":[{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[1,4]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0]}],"complexes":[],"partners":["BNIP3","BNIP3L","METTL1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P17152","full_name":"Transmembrane protein 11, mitochondrial","aliases":["Protein PM1","Protein PMI"],"length_aa":192,"mass_kda":21.5,"function":"Plays a role in mitochondrial morphogenesis","subcellular_location":"Mitochondrion inner membrane","url":"https://www.uniprot.org/uniprotkb/P17152/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TMEM11","classification":"Not Classified","n_dependent_lines":51,"n_total_lines":1208,"dependency_fraction":0.042218543046357616},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"ACTG1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/TMEM11","total_profiled":1310},"omim":[{"mim_id":"618817","title":"TRANSMEMBRANE PROTEIN 11; TMEM11","url":"https://www.omim.org/entry/618817"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Mitochondria","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TMEM11"},"hgnc":{"alias_symbol":["PMI","PM1"],"prev_symbol":["C17orf35"]},"alphafold":{"accession":"P17152","domains":[{"cath_id":"-","chopping":"28-190","consensus_level":"medium","plddt":83.3639,"start":28,"end":190}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P17152","model_url":"https://alphafold.ebi.ac.uk/files/AF-P17152-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P17152-F1-predicted_aligned_error_v6.png","plddt_mean":78.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TMEM11","jax_strain_url":"https://www.jax.org/strain/search?query=TMEM11"},"sequence":{"accession":"P17152","fasta_url":"https://rest.uniprot.org/uniprotkb/P17152.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P17152/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P17152"}},"corpus_meta":[{"pmid":"7745720","id":"PMC_7745720","title":"Growth of macrophage-tropic and primary human immunodeficiency virus type 1 (HIV-1) isolates in a unique CD4+ T-cell clone (PM1): failure to downregulate CD4 and to interfere with cell-line-tropic HIV-1.","date":"1995","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/7745720","citation_count":239,"is_preprint":false},{"pmid":"8368848","id":"PMC_8368848","title":"Purification and characterization of a phenoloxidase (laccase) from the lignin-degrading basidiomycete PM1 (CECT 2971).","date":"1993","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/8368848","citation_count":118,"is_preprint":false},{"pmid":"17158667","id":"PMC_17158667","title":"Whole-genome analysis of the methyl tert-butyl ether-degrading beta-proteobacterium Methylibium petroleiphilum PM1.","date":"2006","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/17158667","citation_count":98,"is_preprint":false},{"pmid":"8285710","id":"PMC_8285710","title":"Characterization and structural analysis of the laccase I gene from the newly isolated ligninolytic basidiomycete PM1 (CECT 2971).","date":"1993","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/8285710","citation_count":67,"is_preprint":false},{"pmid":"12175077","id":"PMC_12175077","title":"Genetic mapping of the Lr20-Pm1 resistance locus reveals suppressed recombination on chromosome arm 7AL in hexaploid wheat.","date":"2002","source":"Genome","url":"https://pubmed.ncbi.nlm.nih.gov/12175077","citation_count":64,"is_preprint":false},{"pmid":"18470129","id":"PMC_18470129","title":"RFLP markers linked to powdery mildew resistance genes Pm1, Pm2, Pm3, and Pm4 in wheat.","date":"1994","source":"Genome","url":"https://pubmed.ncbi.nlm.nih.gov/18470129","citation_count":55,"is_preprint":false},{"pmid":"11679339","id":"PMC_11679339","title":"Detection and quantification of methyl tert-butyl ether-degrading strain PM1 by real-time TaqMan PCR.","date":"2001","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/11679339","citation_count":49,"is_preprint":false},{"pmid":"27086076","id":"PMC_27086076","title":"Assessment of microbial communities in PM1 and PM10 of Urumqi during winter.","date":"2016","source":"Environmental pollution (Barking, Essex : 1987)","url":"https://pubmed.ncbi.nlm.nih.gov/27086076","citation_count":48,"is_preprint":false},{"pmid":"12732529","id":"PMC_12732529","title":"Naturally occurring bacteria similar to the methyl tert-butyl ether (MTBE)-degrading strain PM1 are present in MTBE-contaminated groundwater.","date":"2003","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/12732529","citation_count":47,"is_preprint":false},{"pmid":"37286744","id":"PMC_37286744","title":"TMEM11 regulates cardiomyocyte proliferation and cardiac repair via METTL1-mediated m7G methylation of ATF5 mRNA.","date":"2023","source":"Cell death and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/37286744","citation_count":44,"is_preprint":false},{"pmid":"6334745","id":"PMC_6334745","title":"Clinical relevance of PM-1 antibody and physiochemical characterization of PM-1 antigen.","date":"1984","source":"The Journal of rheumatology","url":"https://pubmed.ncbi.nlm.nih.gov/6334745","citation_count":42,"is_preprint":false},{"pmid":"27726085","id":"PMC_27726085","title":"Chemical characterization of PM1.0 aerosol in Delhi and source apportionment using positive matrix factorization.","date":"2016","source":"Environmental science and pollution research international","url":"https://pubmed.ncbi.nlm.nih.gov/27726085","citation_count":41,"is_preprint":false},{"pmid":"11882715","id":"PMC_11882715","title":"npd gene functions of Rhodococcus (opacus) erythropolis HL PM-1 in the initial steps of 2,4,6-trinitrophenol degradation.","date":"2002","source":"Microbiology (Reading, England)","url":"https://pubmed.ncbi.nlm.nih.gov/11882715","citation_count":41,"is_preprint":false},{"pmid":"21274005","id":"PMC_21274005","title":"Inner-membrane proteins PMI/TMEM11 regulate mitochondrial morphogenesis independently of the DRP1/MFN fission/fusion pathways.","date":"2011","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/21274005","citation_count":39,"is_preprint":false},{"pmid":"26660669","id":"PMC_26660669","title":"Fine mapping of a dominantly inherited powdery mildew resistance major-effect QTL, Pm1.1, in cucumber identifies a 41.1 kb region containing two tandemly arrayed cysteine-rich receptor-like protein kinase genes.","date":"2015","source":"TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik","url":"https://pubmed.ncbi.nlm.nih.gov/26660669","citation_count":39,"is_preprint":false},{"pmid":"17070231","id":"PMC_17070231","title":"The role of nephron sparing surgery for metastatic (pM1) renal cell carcinoma.","date":"2006","source":"The Journal of urology","url":"https://pubmed.ncbi.nlm.nih.gov/17070231","citation_count":39,"is_preprint":false},{"pmid":"22922455","id":"PMC_22922455","title":"Morphology changes in human lung epithelial cells after exposure to diesel exhaust micron sub particles (PM₁.₀) and pollen allergens.","date":"2012","source":"Environmental pollution (Barking, Essex : 1987)","url":"https://pubmed.ncbi.nlm.nih.gov/22922455","citation_count":39,"is_preprint":false},{"pmid":"36795401","id":"PMC_36795401","title":"The outer mitochondrial membrane protein TMEM11 demarcates spatially restricted BNIP3/BNIP3L-mediated mitophagy.","date":"2023","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/36795401","citation_count":37,"is_preprint":false},{"pmid":"28681290","id":"PMC_28681290","title":"Physicochemical properties, in vitro cytotoxic and genotoxic effects of PM1.0 and PM2.5 from Shanghai, China.","date":"2017","source":"Environmental science and pollution research international","url":"https://pubmed.ncbi.nlm.nih.gov/28681290","citation_count":37,"is_preprint":false},{"pmid":"19620231","id":"PMC_19620231","title":"Airborne fungal and bacterial components in PM1 dust from biofuel plants.","date":"2009","source":"The Annals of occupational hygiene","url":"https://pubmed.ncbi.nlm.nih.gov/19620231","citation_count":35,"is_preprint":false},{"pmid":"29667303","id":"PMC_29667303","title":"MiR-146a regulates PM1 -induced inflammation via NF-κB signaling pathway in BEAS-2B cells.","date":"2018","source":"Environmental toxicology","url":"https://pubmed.ncbi.nlm.nih.gov/29667303","citation_count":35,"is_preprint":false},{"pmid":"22230069","id":"PMC_22230069","title":"Inflammatory effects on human lung epithelial cells after exposure to diesel exhaust micron sub particles (PM₁.₀) and pollen allergens.","date":"2011","source":"Environmental pollution (Barking, Essex : 1987)","url":"https://pubmed.ncbi.nlm.nih.gov/22230069","citation_count":35,"is_preprint":false},{"pmid":"29327190","id":"PMC_29327190","title":"Chemical characterization and quantitativ e assessment of source-specific health risk of trace metals in PM1.0 at a road site of Delhi, India.","date":"2018","source":"Environmental science and pollution research international","url":"https://pubmed.ncbi.nlm.nih.gov/29327190","citation_count":35,"is_preprint":false},{"pmid":"23369580","id":"PMC_23369580","title":"Influence of oxygen on NADH recycling and oxidative stress resistance systems in Lactobacillus panis PM1.","date":"2013","source":"AMB Express","url":"https://pubmed.ncbi.nlm.nih.gov/23369580","citation_count":32,"is_preprint":false},{"pmid":"11321538","id":"PMC_11321538","title":"Isolate PM1 populations are dominant and novel methyl tert-butyl ether-degrading bacterial in compost biofilter enrichments.","date":"2001","source":"Environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/11321538","citation_count":30,"is_preprint":false},{"pmid":"30594755","id":"PMC_30594755","title":"Size distribution of bioaerosols from biomass burning emissions: Characteristics of bacterial and fungal communities in submicron (PM1.0) and fine (PM2.5) particles.","date":"2018","source":"Ecotoxicology and environmental safety","url":"https://pubmed.ncbi.nlm.nih.gov/30594755","citation_count":30,"is_preprint":false},{"pmid":"23509745","id":"PMC_23509745","title":"Milan PM1 induces adverse effects on mice lungs and cardiovascular system.","date":"2012","source":"BioMed research international","url":"https://pubmed.ncbi.nlm.nih.gov/23509745","citation_count":29,"is_preprint":false},{"pmid":"15743721","id":"PMC_15743721","title":"Comparison of biostimulation versus bioaugmentation with bacterial strain PM1 for treatment of groundwater contaminated with methyl tertiary butyl ether (MTBE).","date":"2005","source":"Environmental health perspectives","url":"https://pubmed.ncbi.nlm.nih.gov/15743721","citation_count":29,"is_preprint":false},{"pmid":"18791002","id":"PMC_18791002","title":"Involvement of a novel enzyme, MdpA, in methyl tert-butyl ether degradation in Methylibium petroleiphilum PM1.","date":"2008","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/18791002","citation_count":28,"is_preprint":false},{"pmid":"17890343","id":"PMC_17890343","title":"Comparative transcriptome analysis of Methylibium petroleiphilum PM1 exposed to the fuel oxygenates methyl tert-butyl ether and ethanol.","date":"2007","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/17890343","citation_count":27,"is_preprint":false},{"pmid":"27208422","id":"PMC_27208422","title":"Comparative study of the effects of PM1-induced oxidative stress on autophagy and surfactant protein B and C expressions in lung alveolar type II epithelial MLE-12 cells.","date":"2016","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/27208422","citation_count":26,"is_preprint":false},{"pmid":"14679229","id":"PMC_14679229","title":"NpdR, a repressor involved in 2,4,6-trinitrophenol degradation in Rhodococcus opacus HL PM-1.","date":"2004","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/14679229","citation_count":26,"is_preprint":false},{"pmid":"27692295","id":"PMC_27692295","title":"Characterization of urban aerosol: seasonal variation of mutagenicity and genotoxicity of PM2.5, PM1 and semi-volatile organic compounds.","date":"2016","source":"Mutation research. Genetic toxicology and environmental mutagenesis","url":"https://pubmed.ncbi.nlm.nih.gov/27692295","citation_count":26,"is_preprint":false},{"pmid":"23912115","id":"PMC_23912115","title":"Contributions of citrate in redox potential maintenance and ATP production: metabolic pathways and their regulation in Lactobacillus panis PM1.","date":"2013","source":"Applied microbiology and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/23912115","citation_count":25,"is_preprint":false},{"pmid":"29890605","id":"PMC_29890605","title":"Nitro and oxy-PAHs bounded in PM2.5 and PM1.0 under different weather conditions at Mount Tai in Eastern China: Sources, long-distance transport, and cancer risk assessment.","date":"2017","source":"The Science of the total environment","url":"https://pubmed.ncbi.nlm.nih.gov/29890605","citation_count":25,"is_preprint":false},{"pmid":"20395201","id":"PMC_20395201","title":"Ectopic expression of X-linked lymphocyte-regulated protein pM1 renders tumor cells resistant to antitumor immunity.","date":"2010","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/20395201","citation_count":24,"is_preprint":false},{"pmid":"8130927","id":"PMC_8130927","title":"Heterogeneity among neuroepithelial cells in the chick retina revealed by immunostaining with monoclonal antibody PM1.","date":"1994","source":"The European journal of neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/8130927","citation_count":20,"is_preprint":false},{"pmid":"31728947","id":"PMC_31728947","title":"Trace elements and human health risks assessment of finer aerosol atmospheric particles (PM1).","date":"2019","source":"Environmental science and pollution research international","url":"https://pubmed.ncbi.nlm.nih.gov/31728947","citation_count":19,"is_preprint":false},{"pmid":"9786217","id":"PMC_9786217","title":"Heat shock proteins in retinal neurogenesis: identification of the PM1 antigen as the chick Hsc70 and its expression in comparison to that of other chaperones.","date":"1998","source":"The European journal of neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/9786217","citation_count":18,"is_preprint":false},{"pmid":"24096428","id":"PMC_24096428","title":"Regulation of dual glycolytic pathways for fructose metabolism in heterofermentative Lactobacillus panis PM1.","date":"2013","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/24096428","citation_count":17,"is_preprint":false},{"pmid":"19034464","id":"PMC_19034464","title":"The PM1 neurons, movement sensitive centrifugal visual brain neurons in the locust: anatomy, physiology, and modulation by identified octopaminergic neurons.","date":"2008","source":"Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology","url":"https://pubmed.ncbi.nlm.nih.gov/19034464","citation_count":17,"is_preprint":false},{"pmid":"30858030","id":"PMC_30858030","title":"Indirect effect of PM1 on endothelial cells via inducing the release of respiratory inflammatory cytokines.","date":"2019","source":"Toxicology in vitro : an international journal published in association with BIBRA","url":"https://pubmed.ncbi.nlm.nih.gov/30858030","citation_count":16,"is_preprint":false},{"pmid":"28391951","id":"PMC_28391951","title":"Source apportionment of PAHs and n-alkanes bound to PM1 collected near the Venice highway.","date":"2016","source":"Journal of environmental sciences (China)","url":"https://pubmed.ncbi.nlm.nih.gov/28391951","citation_count":16,"is_preprint":false},{"pmid":"29121603","id":"PMC_29121603","title":"Assessment of light extinction at a European polluted urban area during wintertime: Impact of PM1 composition and sources.","date":"2017","source":"Environmental pollution (Barking, Essex : 1987)","url":"https://pubmed.ncbi.nlm.nih.gov/29121603","citation_count":16,"is_preprint":false},{"pmid":"24982222","id":"PMC_24982222","title":"Exposure to submicron particles (PM1.0) from diesel exhaust and pollen allergens of human lung epithelial cells induces morphological changes of mitochondria tonifilaments and rough endoplasmic reticulum.","date":"2014","source":"In vivo (Athens, Greece)","url":"https://pubmed.ncbi.nlm.nih.gov/24982222","citation_count":15,"is_preprint":false},{"pmid":"37268213","id":"PMC_37268213","title":"Does PM1 exposure during pregnancy impact the gut microbiota of mothers and neonates?","date":"2023","source":"Environmental research","url":"https://pubmed.ncbi.nlm.nih.gov/37268213","citation_count":14,"is_preprint":false},{"pmid":"23795775","id":"PMC_23795775","title":"Glycerol and environmental factors: effects on 1,3-propanediol production and NAD(+) regeneration in Lactobacillus panis PM1.","date":"2013","source":"Journal of applied microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/23795775","citation_count":14,"is_preprint":false},{"pmid":"24522935","id":"PMC_24522935","title":"Bioconversion of glycerol to 1,3-propanediol in thin stillage-based media by engineered Lactobacillus panis PM1.","date":"2014","source":"Journal of industrial microbiology & biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/24522935","citation_count":14,"is_preprint":false},{"pmid":"24643332","id":"PMC_24643332","title":"Complete genome sequence of the Pectobacterium carotovorum subsp. carotovorum virulent bacteriophage PM1.","date":"2014","source":"Archives of virology","url":"https://pubmed.ncbi.nlm.nih.gov/24643332","citation_count":14,"is_preprint":false},{"pmid":"33043050","id":"PMC_33043050","title":"Alteration in angiotensin-converting enzyme 2 by PM1 during the development of emphysema in rats.","date":"2020","source":"ERJ open research","url":"https://pubmed.ncbi.nlm.nih.gov/33043050","citation_count":14,"is_preprint":false},{"pmid":"34971641","id":"PMC_34971641","title":"PM1-loaded recombinant human H-ferritin nanocages: A novel pH-responsive sensing platform for the identification of cancer cells.","date":"2021","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/34971641","citation_count":13,"is_preprint":false},{"pmid":"33194559","id":"PMC_33194559","title":"Unraveling the blood transcriptome after real-life exposure of Wistar-rats to PM2.5, PM1 and water-soluble metals in the ambient air.","date":"2020","source":"Toxicology reports","url":"https://pubmed.ncbi.nlm.nih.gov/33194559","citation_count":13,"is_preprint":false},{"pmid":"25281374","id":"PMC_25281374","title":"Metabolic engineering of a glycerol-oxidative pathway in Lactobacillus panis PM1 for utilization of bioethanol thin stillage: potential to produce platform chemicals from glycerol.","date":"2014","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/25281374","citation_count":13,"is_preprint":false},{"pmid":"31138407","id":"PMC_31138407","title":"Characterization of urban aerosol: Seasonal variation of genotoxicity of the water-soluble portion of PM2.5 and PM1.","date":"2019","source":"Mutation research. Genetic toxicology and environmental mutagenesis","url":"https://pubmed.ncbi.nlm.nih.gov/31138407","citation_count":12,"is_preprint":false},{"pmid":"28387856","id":"PMC_28387856","title":"Involvement of C-Terminal Histidines in Soybean PM1 Protein Oligomerization and Cu2+ Binding.","date":"2017","source":"Plant & cell physiology","url":"https://pubmed.ncbi.nlm.nih.gov/28387856","citation_count":11,"is_preprint":false},{"pmid":"38522584","id":"PMC_38522584","title":"Redox-activity and in vitro effects of regional atmospheric aerosol pollution: Seasonal differences and correlation between oxidative potential and in vitro toxicity of PM1.","date":"2024","source":"Toxicology and applied pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/38522584","citation_count":10,"is_preprint":false},{"pmid":"23315235","id":"PMC_23315235","title":"Complete nucleotide sequence of Bacillus subtilis (natto) bacteriophage PM1, a phage associated with disruption of food production.","date":"2013","source":"Virus genes","url":"https://pubmed.ncbi.nlm.nih.gov/23315235","citation_count":10,"is_preprint":false},{"pmid":"28508335","id":"PMC_28508335","title":"Toxic potential of organic constituents of submicron particulate matter (PM1) in an urban road site (Barcelona).","date":"2017","source":"Environmental science and pollution research international","url":"https://pubmed.ncbi.nlm.nih.gov/28508335","citation_count":9,"is_preprint":false},{"pmid":"21112690","id":"PMC_21112690","title":"Aerobic degradation of methyl tert-butyl ether in a closed symbiotic system containing a mixed culture of Chlorella ellipsoidea and Methylibium petroleiphilum PM1.","date":"2010","source":"Journal of hazardous materials","url":"https://pubmed.ncbi.nlm.nih.gov/21112690","citation_count":9,"is_preprint":false},{"pmid":"31494852","id":"PMC_31494852","title":"Source apportionment of urban PM1 in Barcelona during SAPUSS using organic and inorganic components.","date":"2019","source":"Environmental science and pollution research international","url":"https://pubmed.ncbi.nlm.nih.gov/31494852","citation_count":7,"is_preprint":false},{"pmid":"8955064","id":"PMC_8955064","title":"Replication of primary HIV-1 isolates is inhibited in PM1 cells expressing sCD4-KDEL.","date":"1996","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/8955064","citation_count":6,"is_preprint":false},{"pmid":"7696981","id":"PMC_7696981","title":"Domain structure of laccase I from the lignin-degrading basidiomycete PM1 revealed by differential scanning calorimetry.","date":"1994","source":"Biochemistry and molecular biology international","url":"https://pubmed.ncbi.nlm.nih.gov/7696981","citation_count":6,"is_preprint":false},{"pmid":"39770660","id":"PMC_39770660","title":"Bioremediation Potential of Rhodococcus qingshengii PM1 in Sodium Selenite-Contaminated Soil and Its Impact on Microbial Community Assembly.","date":"2024","source":"Microorganisms","url":"https://pubmed.ncbi.nlm.nih.gov/39770660","citation_count":5,"is_preprint":false},{"pmid":"33266174","id":"PMC_33266174","title":"A Possible Role of Insertion Sequence IS1216V in Dissemination of Multidrug-Resistant Elements MESPM1 and MES6272-2 between Enterococcus and ST59 Staphylococcus aureus.","date":"2020","source":"Microorganisms","url":"https://pubmed.ncbi.nlm.nih.gov/33266174","citation_count":5,"is_preprint":false},{"pmid":"25724531","id":"PMC_25724531","title":"Gene mdpC plays a regulatory role in the methyl-tert-butyl ether degradation pathway of Methylibium petroleiphilum strain PM1.","date":"2015","source":"FEMS microbiology letters","url":"https://pubmed.ncbi.nlm.nih.gov/25724531","citation_count":5,"is_preprint":false},{"pmid":"40672531","id":"PMC_40672531","title":"Biodegradation of sodium selenite by a highly tolerant strain Rhodococcus qingshengii PM1: Biochemical characterization and comparative genome analysis.","date":"2025","source":"Current research in microbial sciences","url":"https://pubmed.ncbi.nlm.nih.gov/40672531","citation_count":5,"is_preprint":false},{"pmid":"26591997","id":"PMC_26591997","title":"[Characterizing Beijing's Airborne Bacterial Communities in PM2.5 and PM1 Samples During Haze Pollution Episodes Using 16S rRNA Gene Analysis Method].","date":"2015","source":"Huan jing ke xue= Huanjing kexue","url":"https://pubmed.ncbi.nlm.nih.gov/26591997","citation_count":4,"is_preprint":false},{"pmid":"32756462","id":"PMC_32756462","title":"The N-Terminal Region of Soybean PM1 Protein Protects Liposomes during Freeze-Thaw.","date":"2020","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/32756462","citation_count":3,"is_preprint":false},{"pmid":"35987247","id":"PMC_35987247","title":"Apportioning PM1 in a contrasting receptor site in the Mediterranean region: Aerosol sources with an updated sulfur speciation.","date":"2022","source":"The Science of the total environment","url":"https://pubmed.ncbi.nlm.nih.gov/35987247","citation_count":3,"is_preprint":false},{"pmid":"37717746","id":"PMC_37717746","title":"Submicronic particulate matter (PM1), a \"neglected killer\" for HIV/AIDS patients in Hubei, China: Results from a cohort study from 2001 to 2020.","date":"2023","source":"The Science of the total environment","url":"https://pubmed.ncbi.nlm.nih.gov/37717746","citation_count":3,"is_preprint":false},{"pmid":"33094390","id":"PMC_33094390","title":"Characterization of ambient PM1 at a suburban site of Agra: chemical composition, sources, health risk and potential cytotoxicity.","date":"2020","source":"Environmental geochemistry and health","url":"https://pubmed.ncbi.nlm.nih.gov/33094390","citation_count":3,"is_preprint":false},{"pmid":"15283333","id":"PMC_15283333","title":"[Degradation of 2,4-dinitrophenol by free and immobilized cells of Rhodococcus erythropolis HL PM-1].","date":"2004","source":"Prikladnaia biokhimiia i mikrobiologiia","url":"https://pubmed.ncbi.nlm.nih.gov/15283333","citation_count":3,"is_preprint":false},{"pmid":"36930241","id":"PMC_36930241","title":"Fine-tune TMEM11 to unleash basal mitophagy.","date":"2023","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/36930241","citation_count":2,"is_preprint":false},{"pmid":"35841497","id":"PMC_35841497","title":"Pseudomonas aeruginosa isolate PM1 effectively controls virus infection and promotes growth in plants.","date":"2022","source":"Archives of microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/35841497","citation_count":2,"is_preprint":false},{"pmid":"40390499","id":"PMC_40390499","title":"Whole genome analysis of endophytic strain PM1 reveals promising plant Growth-Promoting mechanisms in pomegranate.","date":"2025","source":"Journal, genetic engineering & biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/40390499","citation_count":2,"is_preprint":false},{"pmid":"24563308","id":"PMC_24563308","title":"Transcriptional repressor role of PocR on the 1,3-propanediol biosynthetic pathway by Lactobacillus panis PM1.","date":"2014","source":"Biotechnology letters","url":"https://pubmed.ncbi.nlm.nih.gov/24563308","citation_count":2,"is_preprint":false},{"pmid":"23831510","id":"PMC_23831510","title":"Structural and kinetic characterization of two 4-oxalocrotonate tautomerases in Methylibium petroleiphilum strain PM1.","date":"2013","source":"Archives of biochemistry and biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/23831510","citation_count":2,"is_preprint":false},{"pmid":"41570932","id":"PMC_41570932","title":"TMEM11 promotes cisplatin resistance by inhibiting BNIP3-mediated mitophagy in bladder cancer.","date":"2026","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/41570932","citation_count":1,"is_preprint":false},{"pmid":"41017653","id":"PMC_41017653","title":"HCSeeker: A classification tool for human genetic variant hot and cold spots designed for PM1 and benign criteria in the ACMG-AMP guideline.","date":"2025","source":"Genetics in medicine : official journal of the American College of Medical Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/41017653","citation_count":1,"is_preprint":false},{"pmid":"26204003","id":"PMC_26204003","title":"Nosema sp. PM-1, a new isolate of microsporidian from infected Papilio machaon Linnaeus, based on ultrastructure and molecular identification.","date":"2015","source":"Acta parasitologica","url":"https://pubmed.ncbi.nlm.nih.gov/26204003","citation_count":1,"is_preprint":false},{"pmid":"39149412","id":"PMC_39149412","title":"Both Splice Variants of Zebrafish Tmem11 Localize to the Outer Membrane of Mitochondria.","date":"2024","source":"microPublication biology","url":"https://pubmed.ncbi.nlm.nih.gov/39149412","citation_count":0,"is_preprint":false},{"pmid":"41165114","id":"PMC_41165114","title":"Complete genome sequence of Enterococcus faecium PM1 isolated from a diseased broiler breeder.","date":"2025","source":"Microbiology resource announcements","url":"https://pubmed.ncbi.nlm.nih.gov/41165114","citation_count":0,"is_preprint":false},{"pmid":"40871448","id":"PMC_40871448","title":"Isolation and Characterization of the Trimethylamine (TMA)-Degrading Microbacterium lacticum Strain PM-1.","date":"2025","source":"Microorganisms","url":"https://pubmed.ncbi.nlm.nih.gov/40871448","citation_count":0,"is_preprint":false},{"pmid":"41879646","id":"PMC_41879646","title":"Crystal structure of PM1Pgh, a poly-γ-glutamate hydrolase from Bacillus phage PM1.","date":"2026","source":"Acta crystallographica. Section F, Structural biology communications","url":"https://pubmed.ncbi.nlm.nih.gov/41879646","citation_count":0,"is_preprint":false},{"pmid":"41967747","id":"PMC_41967747","title":"Pre-diagnosis and post-treatment exposures to PM1, PM2.5, and PM10 and breast cancer survival: A cohort study.","date":"2026","source":"Environmental research","url":"https://pubmed.ncbi.nlm.nih.gov/41967747","citation_count":0,"is_preprint":false},{"pmid":"41792595","id":"PMC_41792595","title":"Evaluating Proteus mirabilis phage vB_PmiA_PM1 efficacy against catheter-associated urinary tract infections in artificial urine and laboratory media.","date":"2026","source":"BMC microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/41792595","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.08.30.673081","title":"Engineering  <i>Escherichia coli</i>  Nissle as safe chassis for delivery of therapeutic peptides","date":"2025-08-30","source":"bioRxiv","url":"https://doi.org/10.1101/2025.08.30.673081","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.08.25.25334371","title":"Multi-Platform Curation in the Development of ACMG/AMP Specifications for Von Hippel Lindau (VHL) Disease","date":"2025-08-27","source":"bioRxiv","url":"https://doi.org/10.1101/2025.08.25.25334371","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.07.28.25332296","title":"Mapping the association between environmental pollutants and steatotic liver disease: a systematic review and meta-analysis","date":"2025-07-28","source":"bioRxiv","url":"https://doi.org/10.1101/2025.07.28.25332296","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":45201,"output_tokens":1628,"usd":0.080011,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8398,"output_tokens":2294,"usd":0.04967,"stage2_stop_reason":"end_turn"},"total_usd":0.129681,"stage1_batch_id":"msgbatch_017qqVz33Ga63SCDwzb35XPb","stage2_batch_id":"msgbatch_01Scr2Ei9x4HJMiRGxwrmvLK","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"Drosophila PMI (ortholog of human TMEM11) encodes a mitochondrial inner-membrane protein that regulates mitochondrial morphogenesis. Loss of PMI causes a highly condensed mitochondrial network, indicating a pro-fission or anti-fusion function. Genetic epistasis experiments showed this effect is independent of drp1 (DRP1) and mfn (Mitofusin), establishing a separate pathway for mitochondrial network shaping.\",\n      \"method\": \"Genetic loss-of-function (PMI mutant cells), epistasis analysis (double mutants with drp1 and mfn), subcellular localization of endogenous protein\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal genetic epistasis with two independent pathways, direct localization, clean loss-of-function phenotype, published in peer-reviewed journal\",\n      \"pmids\": [\"21274005\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TMEM11 forms a complex with BNIP3 and BNIP3L (outer mitochondrial membrane receptor proteins) and co-enriches at sites of mitophagosome formation. Loss of TMEM11 results in hyper-active BNIP3/BNIP3L-mediated mitophagy during both normoxia and hypoxia-mimetic conditions due to an increase in the number of BNIP3/BNIP3L mitophagy sites, supporting a model where TMEM11 spatially restricts mitophagosome formation.\",\n      \"method\": \"Co-immunoprecipitation (TMEM11 complex with BNIP3/BNIP3L), fluorescence co-localization at mitophagy sites, TMEM11 knockout cells with quantitative mitophagy assays under normoxia and hypoxia-mimetic conditions\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, quantitative mitophagy assays in KO cells, spatial co-localization, two orthogonal methods, peer-reviewed\",\n      \"pmids\": [\"36795401\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TMEM11 directly interacts with METTL1 and enhances m7G methylation of Atf5 mRNA, thereby increasing ATF5 protein expression. Elevated ATF5 promotes transcription of Inca1 (an inhibitor of cyclin-dependent kinase interacting with cyclin A1), which suppresses cardiomyocyte proliferation. TMEM11 deletion enhanced cardiomyocyte proliferation and restored heart function after myocardial injury; TMEM11 overexpression had the opposite effect.\",\n      \"method\": \"Co-immunoprecipitation (TMEM11-METTL1 interaction), m7G methylation assay of Atf5 mRNA, loss-of-function (TMEM11 deletion) and gain-of-function (TMEM11 overexpression) in cardiomyocytes and mouse hearts, ATF5 reporter/expression analysis, Inca1 transcription assay\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — Co-IP, mRNA methylation assay, in vitro and in vivo loss- and gain-of-function with defined molecular pathway, multiple orthogonal methods in single study\",\n      \"pmids\": [\"37286744\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Both splice variants of zebrafish Tmem11 localize to the outer membrane of mitochondria, as determined by fluorescent tagging in cell culture and biochemical membrane fractionation. This contrasts with the previously reported inner-membrane localization in Drosophila but is consistent with the outer mitochondrial membrane localization reported in mammalian studies.\",\n      \"method\": \"Fluorescent protein fusion (live imaging in cell culture), biochemical fractionation of mitochondrial membranes\",\n      \"journal\": \"microPublication biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with two orthogonal methods (imaging + fractionation), single lab, zebrafish ortholog\",\n      \"pmids\": [\"39149412\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"TMEM11 inhibits BNIP3-mediated mitophagy and apoptosis in bladder cancer cells, stabilizing mitochondrial function to promote cisplatin resistance. Mechanistically, TMEM11 suppresses BNIP3 expression and impairs mitophagy flux. TMEM11 knockdown reduced tumor growth and sensitized tumors to cisplatin in vivo.\",\n      \"method\": \"TMEM11 knockdown (siRNA/shRNA), mitophagy flux assays, apoptosis assays, BNIP3 expression analysis, in vivo xenograft with cisplatin treatment, molecular docking (Curcumin as TMEM11 inhibitor)\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined molecular phenotype (BNIP3 suppression, mitophagy flux), in vitro and in vivo validation, single lab\",\n      \"pmids\": [\"41570932\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TMEM11 is an outer mitochondrial membrane protein that (1) regulates mitochondrial network morphology through a pathway independent of DRP1/Mitofusin fission-fusion machinery, (2) spatially restricts BNIP3/BNIP3L-mediated receptor mitophagy by forming a complex with these receptors and limiting mitophagosome formation sites, (3) interacts with METTL1 to enhance m7G methylation of ATF5 mRNA, promoting ATF5-INCA1 axis-mediated suppression of cardiomyocyte proliferation, and (4) suppresses BNIP3-mediated mitophagy flux to modulate cisplatin resistance in cancer cells.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TMEM11 is a mitochondrial membrane protein that shapes mitochondrial network morphology and constrains receptor-mediated mitophagy [#0, #1]. It localizes to the outer mitochondrial membrane [#3] and regulates network morphology through a pathway genetically separable from the canonical DRP1/Mitofusin fission–fusion machinery, since loss of its Drosophila ortholog PMI produces a condensed network independent of drp1 and mfn [#0]. At the mitophagy interface, TMEM11 forms a complex with the outer-membrane receptor proteins BNIP3 and BNIP3L and co-enriches at sites of mitophagosome formation; its loss increases the number of mitophagy sites and hyperactivates BNIP3/BNIP3L-driven mitophagy under both normoxia and hypoxia-mimetic conditions, establishing TMEM11 as a spatial restrictor of mitophagosome nucleation [#1]. This BNIP3-suppressing activity has disease relevance: in bladder cancer cells TMEM11 suppresses BNIP3 expression and impairs mitophagy flux to stabilize mitochondria and promote cisplatin resistance [#4]. Independent of its membrane role, TMEM11 interacts with the m7G methyltransferase METTL1 to enhance m7G methylation of Atf5 mRNA, raising ATF5 protein and driving an ATF5–INCA1 axis that suppresses cardiomyocyte proliferation [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Established that TMEM11/PMI controls mitochondrial network shape through a pathway distinct from the known fission–fusion machinery, defining a novel morphogenesis regulator.\",\n      \"evidence\": \"Genetic loss-of-function and reciprocal epistasis with drp1 and mfn plus endogenous localization in Drosophila\",\n      \"pmids\": [\"21274005\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular activity producing the condensed-network phenotype not defined\", \"Inner-membrane localization in Drosophila later contradicted by outer-membrane reports in other species\", \"No direct partners identified at this stage\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Answered how TMEM11 intersects with selective mitophagy, showing it physically partners with BNIP3/BNIP3L and spatially limits where mitophagosomes form.\",\n      \"evidence\": \"Reciprocal Co-IP, fluorescence co-localization at mitophagy sites, and quantitative mitophagy assays in KO cells under normoxia and hypoxia-mimetic conditions\",\n      \"pmids\": [\"36795401\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis for restricting site number unknown\", \"Relationship between morphology role and mitophagy site control not resolved\", \"Whether the BNIP3/BNIP3L complex requires additional subunits unaddressed\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Revealed an unexpected non-morphology function in which TMEM11 acts through METTL1-dependent mRNA modification to control a proliferation-suppressing transcriptional axis.\",\n      \"evidence\": \"Co-IP of TMEM11–METTL1, m7G methylation assay of Atf5 mRNA, and in vitro/in vivo loss- and gain-of-function in cardiomyocytes with ATF5–INCA1 readouts\",\n      \"pmids\": [\"37286744\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How an outer-membrane protein engages a methyltransferase acting on mRNA is mechanistically unexplained\", \"Whether this links to TMEM11's mitochondrial functions unknown\", \"Direct binding interface with METTL1 not mapped\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Resolved the localization discrepancy by placing TMEM11 at the outer mitochondrial membrane, consistent with its mitophagy-receptor partnerships.\",\n      \"evidence\": \"Fluorescent fusion live imaging and biochemical membrane fractionation of both zebrafish Tmem11 splice variants\",\n      \"pmids\": [\"39149412\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab, ortholog-based\", \"Topology and membrane-spanning architecture not defined\", \"Does not reconcile with earlier Drosophila inner-membrane report mechanistically\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Extended the BNIP3-restricting function to a disease context, showing TMEM11 suppresses mitophagy to drive chemoresistance.\",\n      \"evidence\": \"TMEM11 knockdown with mitophagy flux and apoptosis assays, BNIP3 expression analysis, and in vivo xenograft cisplatin sensitization in bladder cancer\",\n      \"pmids\": [\"41570932\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Mechanism of BNIP3 expression suppression versus the earlier spatial-restriction model not reconciled\", \"Curcumin as TMEM11 inhibitor only by docking, not validated biochemically\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular activity that lets TMEM11 both shape mitochondrial networks and gate mitophagosome formation, and how this reconciles with its METTL1/m7G role, remains undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural or enzymatic activity assigned to TMEM11\", \"Unclear whether morphology, mitophagy, and m7G functions share a common mechanism\", \"No reconciliation of suppressing BNIP3 expression versus restricting BNIP3 site number\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [1, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005741\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0, 1, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [1, 4]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"BNIP3\", \"BNIP3L\", \"METTL1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":5,"faith_total":5,"faith_pct":100.0}}