{"gene":"MRPL45","run_date":"2026-06-10T02:59:51","timeline":{"discoveries":[{"year":1996,"finding":"Mba1 (MRPL45) is a mitochondrial inner membrane-associated protein required for biogenesis of the respiratory chain; its overexpression suppresses afg3-null and rca1-null mutations, and its disruption leads to reduced cytochrome b and aa3 levels and a partial respiratory growth defect. The protein is extractable by carbonate but not high salt, indicating peripheral membrane association.","method":"Genetic epistasis (multicopy suppressor screen), gene disruption, c-myc tagging and subcellular fractionation","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with defined phenotype and fractionation, single lab but multiple orthogonal methods","pmids":["8690083"],"is_preprint":false},{"year":2001,"finding":"Mba1 (MRPL45) specifically interacts with mitochondrial translation products and with conservatively sorted, nuclear-encoded proteins during their integration into the inner membrane; it functions as part of the mitochondrial protein export machinery in an Oxa1-independent insertion pathway, with overlapping substrate specificity with Oxa1.","method":"Co-immunoprecipitation/pulldown of translation products, genetic interaction analysis (double mutants), import assays","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal interaction data, genetic epistasis, import assays; replicated and extended in subsequent independent studies","pmids":["11381092"],"is_preprint":false},{"year":2006,"finding":"Mba1 (MRPL45) binds to the large subunit of mitochondrial ribosomes via the inner membrane, functioning as a ribosome receptor that cooperates with the C-terminal ribosome-binding domain of Oxa1 to position the ribosome exit site at the inner membrane insertion machinery. In the absence of both Mba1 and the Oxa1 C-terminus, mitochondrial translation products fail to be properly inserted and become substrates of the matrix chaperone Hsp70.","method":"Co-immunoprecipitation (ribosome binding), double mutant analysis, Hsp70 substrate trapping","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, genetic epistasis with defined molecular phenotype, replicated across multiple studies","pmids":["16601683"],"is_preprint":false},{"year":2010,"finding":"Simultaneous loss of Mba1 (MRPL45) and Mdm38 causes severe defects in biogenesis of cytochrome reductase and cytochrome oxidase due to mis-regulation of Cox1 and cytochrome b mRNA translation, not due to impaired membrane binding of ribosomes; the Cox1 expression defect is rescued by replacing Cox1-specific mRNA regulatory regions, indicating Mba1 and Mdm38 have overlapping regulatory functions in translation of selected mitochondrial mRNAs.","method":"Double mutant analysis, ribosome-membrane fractionation, mRNA chimera rescue experiments","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic epistasis with defined mechanistic rescue, multiple orthogonal methods, independent lab replication","pmids":["20427570"],"is_preprint":false},{"year":2016,"finding":"Mba1 (MRPL45) forms a complex with the scaffold protein Cox20 and translating mitochondrial ribosomes in a Cox2-dependent manner; Mba1 stabilizes the Cox20-ribosome complex and supports cotranslational maturation and handover of nascent Cox2 to the Cox18 tail-export machinery. Mba1 is absent from the Cox20-Cox18 complex, indicating it escorts Cox2 from the insertion machinery to maturing assembly intermediates but does not accompany the C-terminal export step.","method":"Co-immunoprecipitation, mass spectrometry, genetic interaction (Cox18 loss-of-function), ribosome-nascent chain pull-down","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, MS validation, genetic perturbation with defined stage-specific phenotype, single lab but multiple orthogonal methods","pmids":["27550809"],"is_preprint":false},{"year":2018,"finding":"Mba1 (MRPL45) and the newly identified inner membrane protein Mrx15 both interact via soluble C-terminal domains with the large ribosomal subunit and contact mitochondrial translation products during synthesis; they play overlapping roles in cotranslational protein insertion, together organizing membrane protein biogenesis in mitochondria.","method":"Systematic mass spectrometry-based interaction screen, co-immunoprecipitation, translation product cross-linking","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — MS-based interaction mapping combined with Co-IP and functional analysis, multiple orthogonal methods in single study","pmids":["30091672"],"is_preprint":false}],"current_model":"MRPL45 (Mba1/mL45) is a peripheral inner mitochondrial membrane protein that functions as a ribosome receptor, binding the large subunit of mitochondrial ribosomes to tether them at the inner membrane insertion machinery; it cooperates with and partially overlaps Oxa1 and Mdm38 in cotranslational insertion of hydrophobic respiratory chain subunits, stabilizes the Cox20-ribosome complex for Cox2 maturation, and also regulates the translation of selected mitochondrial mRNAs (particularly Cox1 and cytochrome b) through a distinct, translation-regulatory function shared with Mdm38."},"narrative":{"mechanistic_narrative":"MRPL45 (yeast Mba1/mL45) is a peripheral inner mitochondrial membrane protein that couples mitochondrial translation to cotranslational membrane insertion of respiratory chain subunits [PMID:8690083, PMID:16601683]. It is required for respiratory chain biogenesis, and its loss reduces cytochrome b and aa3 levels while producing a partial respiratory growth defect; it associates with the inner membrane through carbonate-extractable, peripheral binding [PMID:8690083]. Mechanistically, MRPL45 acts as a ribosome receptor that binds the large subunit of the mitochondrial ribosome and cooperates with the C-terminal ribosome-binding domain of Oxa1 to position the ribosomal exit site at the inner-membrane insertion machinery; loss of both MRPL45 and the Oxa1 C-terminus leaves nascent translation products uninserted and routes them to matrix Hsp70 [PMID:11381092, PMID:16601683]. It contacts translation products and conservatively sorted nuclear-encoded proteins during their integration, defining an Oxa1-independent insertion route with overlapping substrate specificity, a role shared with the inner membrane protein Mrx15 [PMID:11381092, PMID:30091672]. Beyond insertion, MRPL45 stabilizes a Cox20-ribosome complex in a Cox2-dependent manner and escorts nascent Cox2 toward the Cox18 tail-export machinery without joining the Cox20-Cox18 complex [PMID:27550809]. Independent of ribosome membrane tethering, MRPL45 also functions with Mdm38 to regulate translation of selected mitochondrial mRNAs, including Cox1 and cytochrome b [PMID:20427570].","teleology":[{"year":1996,"claim":"Established that MRPL45/Mba1 is a peripheral inner membrane protein needed for respiratory chain assembly, framing it as a biogenesis factor rather than a structural ribosomal component.","evidence":"Multicopy suppressor screen, gene disruption, c-myc tagging and subcellular fractionation in yeast","pmids":["8690083"],"confidence":"Medium","gaps":["Did not define molecular partners or the step in biogenesis affected","Mode of membrane association characterized only operationally by extraction behavior"]},{"year":2001,"claim":"Showed MRPL45 contacts mitochondrial translation products and nuclear-encoded conservatively sorted proteins during membrane integration, placing it in an Oxa1-independent insertion pathway and answering what process it serves.","evidence":"Co-IP/pulldown of translation products, double-mutant genetic analysis, import assays","pmids":["11381092"],"confidence":"High","gaps":["Did not resolve whether interaction with ribosomes is direct or via nascent chains","Substrate selectivity versus Oxa1 not fully delineated"]},{"year":2006,"claim":"Defined the molecular role as a ribosome receptor binding the mitoribosome large subunit and cooperating with the Oxa1 C-terminus to align the exit tunnel with the insertion machinery.","evidence":"Ribosome-binding Co-IP, double-mutant analysis, Hsp70 substrate trapping in yeast","pmids":["16601683"],"confidence":"High","gaps":["Structural basis of ribosome contact not resolved","Functional redundancy with other receptors not yet identified"]},{"year":2010,"claim":"Separated MRPL45's ribosome-tethering role from a distinct translation-regulatory function, showing that combined loss with Mdm38 mis-regulates Cox1 and cytochrome b mRNA translation independent of ribosome membrane binding.","evidence":"Double-mutant analysis, ribosome-membrane fractionation, mRNA chimera rescue experiments","pmids":["20427570"],"confidence":"High","gaps":["Molecular basis of mRNA-specific regulation unknown","Whether MRPL45 binds the regulatory mRNA regions directly not established"]},{"year":2016,"claim":"Connected MRPL45 to a specific maturation pathway by showing it stabilizes a Cox20-ribosome complex and escorts nascent Cox2 toward the Cox18 export machinery without entering the Cox20-Cox18 step.","evidence":"Co-IP, mass spectrometry, Cox18 genetic perturbation, ribosome-nascent chain pulldown","pmids":["27550809"],"confidence":"High","gaps":["Hand-off mechanism between insertion and Cox18 export not structurally defined","Whether this role generalizes beyond Cox2 unclear"]},{"year":2018,"claim":"Showed MRPL45 acts in parallel with the inner membrane protein Mrx15, both contacting the large ribosomal subunit via soluble C-terminal domains, establishing a redundant network organizing cotranslational membrane protein biogenesis.","evidence":"Systematic MS interaction screen, Co-IP, translation product cross-linking","pmids":["30091672"],"confidence":"High","gaps":["Division of labor between MRPL45 and Mrx15 across substrates not resolved","Structural arrangement of the combined ribosome-membrane interface unknown"]},{"year":null,"claim":"How MRPL45 mechanistically distinguishes its ribosome-tethering insertion function from its mRNA-selective translation-regulatory function, and the structural basis of its ribosome and membrane contacts, remain open.","evidence":"","pmids":[],"confidence":"High","gaps":["No structure of MRPL45 on the mitoribosome at the insertion site","Direct mRNA or regulatory-factor binding not demonstrated"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[2,5]},{"term_id":"GO:0045182","term_label":"translation regulator activity","supporting_discovery_ids":[3]}],"localization":[],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[1,2,4]},{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[3]}],"complexes":["mitochondrial large ribosomal subunit","Cox20-ribosome complex"],"partners":["OXA1","MDM38","COX20","COX18","MRX15"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9BRJ2","full_name":"Large ribosomal subunit protein mL45","aliases":["39S ribosomal protein L45, mitochondrial","L45mt","MRP-L45"],"length_aa":306,"mass_kda":35.4,"function":"Component of the mitochondrial large ribosomal subunit (mt-LSU) (PubMed:25278503, PubMed:25838379, PubMed:28892042, PubMed:33602856, PubMed:35177605). Within the mitochondrial ribosomes, required to direct the nascent polypeptide toward the tunnel exit and position the exit at a distance from the membrane surface (PubMed:33602856)","subcellular_location":"Mitochondrion","url":"https://www.uniprot.org/uniprotkb/Q9BRJ2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/MRPL45","classification":"Common Essential","n_dependent_lines":1067,"n_total_lines":1208,"dependency_fraction":0.8832781456953642},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/MRPL45","total_profiled":1310},"omim":[{"mim_id":"620646","title":"COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 59; COXPD59","url":"https://www.omim.org/entry/620646"},{"mim_id":"611850","title":"MITOCHONDRIAL RIBOSOMAL PROTEIN L45; MRPL45","url":"https://www.omim.org/entry/611850"},{"mim_id":"611845","title":"MITOCHONDRIAL RIBOSOMAL PROTEIN L39; MRPL39","url":"https://www.omim.org/entry/611845"},{"mim_id":"611836","title":"MITOCHONDRIAL RIBOSOMAL PROTEIN L24; MRPL24","url":"https://www.omim.org/entry/611836"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Mitochondria","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/MRPL45"},"hgnc":{"alias_symbol":["MGC11321","Mba1","mL45"],"prev_symbol":[]},"alphafold":{"accession":"Q9BRJ2","domains":[{"cath_id":"3.10.450.240","chopping":"103-266","consensus_level":"high","plddt":91.2496,"start":103,"end":266}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BRJ2","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BRJ2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BRJ2-F1-predicted_aligned_error_v6.png","plddt_mean":80.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MRPL45","jax_strain_url":"https://www.jax.org/strain/search?query=MRPL45"},"sequence":{"accession":"Q9BRJ2","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BRJ2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BRJ2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BRJ2"}},"corpus_meta":[{"pmid":"16601683","id":"PMC_16601683","title":"Mba1, a membrane-associated ribosome receptor in mitochondria.","date":"2006","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/16601683","citation_count":120,"is_preprint":false},{"pmid":"11381092","id":"PMC_11381092","title":"Mba1, a novel component of the mitochondrial protein export machinery of the yeast Saccharomyces cerevisiae.","date":"2001","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/11381092","citation_count":81,"is_preprint":false},{"pmid":"20427570","id":"PMC_20427570","title":"Ribosome-binding proteins Mdm38 and Mba1 display overlapping functions for regulation of mitochondrial translation.","date":"2010","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/20427570","citation_count":53,"is_preprint":false},{"pmid":"30091672","id":"PMC_30091672","title":"The ribosome receptors Mrx15 and Mba1 jointly organize cotranslational insertion and protein biogenesis in mitochondria.","date":"2018","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/30091672","citation_count":28,"is_preprint":false},{"pmid":"16691494","id":"PMC_16691494","title":"Tissue inhibitor of matrix metalloproteinase-1 suppresses apoptosis of mouse bone marrow stromal cell line MBA-1.","date":"2006","source":"Calcified tissue international","url":"https://pubmed.ncbi.nlm.nih.gov/16691494","citation_count":21,"is_preprint":false},{"pmid":"8690083","id":"PMC_8690083","title":"MBA1 encodes a mitochondrial membrane-associated protein required for biogenesis of the respiratory chain.","date":"1996","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/8690083","citation_count":19,"is_preprint":false},{"pmid":"37428039","id":"PMC_37428039","title":"Mitochondrial Membrane-Associated Protein Mba1 Confers Antifungal Resistance by Affecting the Production of Reactive Oxygen Species in Aspergillus fumigatus.","date":"2023","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/37428039","citation_count":18,"is_preprint":false},{"pmid":"27550809","id":"PMC_27550809","title":"Ribosome-Associated Mba1 Escorts Cox2 from Insertion Machinery to Maturing Assembly Intermediates.","date":"2016","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/27550809","citation_count":18,"is_preprint":false},{"pmid":"36829306","id":"PMC_36829306","title":"The Mba1 homologue of Trypanosoma brucei is involved in the biogenesis of oxidative phosphorylation complexes.","date":"2023","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/36829306","citation_count":8,"is_preprint":false},{"pmid":"30207146","id":"PMC_30207146","title":"[Genome analysis of Acidiplasma sp. MBA-1, a polyextremophilic archaeon predominant in the microbial community of a bioleaching reactor].","date":"2017","source":"Mikrobiologiia","url":"https://pubmed.ncbi.nlm.nih.gov/30207146","citation_count":3,"is_preprint":false},{"pmid":"16562667","id":"PMC_16562667","title":"[Apoptosis of mesenchymal cell line MBA-1 induced by core binding factor alpha 1].","date":"2006","source":"Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences","url":"https://pubmed.ncbi.nlm.nih.gov/16562667","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6557,"output_tokens":1593,"usd":0.021783,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8469,"output_tokens":2452,"usd":0.051823,"stage2_stop_reason":"end_turn"},"total_usd":0.073606,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1996,\n      \"finding\": \"Mba1 (MRPL45) is a mitochondrial inner membrane-associated protein required for biogenesis of the respiratory chain; its overexpression suppresses afg3-null and rca1-null mutations, and its disruption leads to reduced cytochrome b and aa3 levels and a partial respiratory growth defect. The protein is extractable by carbonate but not high salt, indicating peripheral membrane association.\",\n      \"method\": \"Genetic epistasis (multicopy suppressor screen), gene disruption, c-myc tagging and subcellular fractionation\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with defined phenotype and fractionation, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"8690083\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Mba1 (MRPL45) specifically interacts with mitochondrial translation products and with conservatively sorted, nuclear-encoded proteins during their integration into the inner membrane; it functions as part of the mitochondrial protein export machinery in an Oxa1-independent insertion pathway, with overlapping substrate specificity with Oxa1.\",\n      \"method\": \"Co-immunoprecipitation/pulldown of translation products, genetic interaction analysis (double mutants), import assays\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal interaction data, genetic epistasis, import assays; replicated and extended in subsequent independent studies\",\n      \"pmids\": [\"11381092\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Mba1 (MRPL45) binds to the large subunit of mitochondrial ribosomes via the inner membrane, functioning as a ribosome receptor that cooperates with the C-terminal ribosome-binding domain of Oxa1 to position the ribosome exit site at the inner membrane insertion machinery. In the absence of both Mba1 and the Oxa1 C-terminus, mitochondrial translation products fail to be properly inserted and become substrates of the matrix chaperone Hsp70.\",\n      \"method\": \"Co-immunoprecipitation (ribosome binding), double mutant analysis, Hsp70 substrate trapping\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, genetic epistasis with defined molecular phenotype, replicated across multiple studies\",\n      \"pmids\": [\"16601683\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Simultaneous loss of Mba1 (MRPL45) and Mdm38 causes severe defects in biogenesis of cytochrome reductase and cytochrome oxidase due to mis-regulation of Cox1 and cytochrome b mRNA translation, not due to impaired membrane binding of ribosomes; the Cox1 expression defect is rescued by replacing Cox1-specific mRNA regulatory regions, indicating Mba1 and Mdm38 have overlapping regulatory functions in translation of selected mitochondrial mRNAs.\",\n      \"method\": \"Double mutant analysis, ribosome-membrane fractionation, mRNA chimera rescue experiments\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic epistasis with defined mechanistic rescue, multiple orthogonal methods, independent lab replication\",\n      \"pmids\": [\"20427570\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Mba1 (MRPL45) forms a complex with the scaffold protein Cox20 and translating mitochondrial ribosomes in a Cox2-dependent manner; Mba1 stabilizes the Cox20-ribosome complex and supports cotranslational maturation and handover of nascent Cox2 to the Cox18 tail-export machinery. Mba1 is absent from the Cox20-Cox18 complex, indicating it escorts Cox2 from the insertion machinery to maturing assembly intermediates but does not accompany the C-terminal export step.\",\n      \"method\": \"Co-immunoprecipitation, mass spectrometry, genetic interaction (Cox18 loss-of-function), ribosome-nascent chain pull-down\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, MS validation, genetic perturbation with defined stage-specific phenotype, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"27550809\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Mba1 (MRPL45) and the newly identified inner membrane protein Mrx15 both interact via soluble C-terminal domains with the large ribosomal subunit and contact mitochondrial translation products during synthesis; they play overlapping roles in cotranslational protein insertion, together organizing membrane protein biogenesis in mitochondria.\",\n      \"method\": \"Systematic mass spectrometry-based interaction screen, co-immunoprecipitation, translation product cross-linking\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — MS-based interaction mapping combined with Co-IP and functional analysis, multiple orthogonal methods in single study\",\n      \"pmids\": [\"30091672\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MRPL45 (Mba1/mL45) is a peripheral inner mitochondrial membrane protein that functions as a ribosome receptor, binding the large subunit of mitochondrial ribosomes to tether them at the inner membrane insertion machinery; it cooperates with and partially overlaps Oxa1 and Mdm38 in cotranslational insertion of hydrophobic respiratory chain subunits, stabilizes the Cox20-ribosome complex for Cox2 maturation, and also regulates the translation of selected mitochondrial mRNAs (particularly Cox1 and cytochrome b) through a distinct, translation-regulatory function shared with Mdm38.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MRPL45 (yeast Mba1/mL45) is a peripheral inner mitochondrial membrane protein that couples mitochondrial translation to cotranslational membrane insertion of respiratory chain subunits [#0, #2]. It is required for respiratory chain biogenesis, and its loss reduces cytochrome b and aa3 levels while producing a partial respiratory growth defect; it associates with the inner membrane through carbonate-extractable, peripheral binding [#0]. Mechanistically, MRPL45 acts as a ribosome receptor that binds the large subunit of the mitochondrial ribosome and cooperates with the C-terminal ribosome-binding domain of Oxa1 to position the ribosomal exit site at the inner-membrane insertion machinery; loss of both MRPL45 and the Oxa1 C-terminus leaves nascent translation products uninserted and routes them to matrix Hsp70 [#1, #2]. It contacts translation products and conservatively sorted nuclear-encoded proteins during their integration, defining an Oxa1-independent insertion route with overlapping substrate specificity, a role shared with the inner membrane protein Mrx15 [#1, #5]. Beyond insertion, MRPL45 stabilizes a Cox20-ribosome complex in a Cox2-dependent manner and escorts nascent Cox2 toward the Cox18 tail-export machinery without joining the Cox20-Cox18 complex [#4]. Independent of ribosome membrane tethering, MRPL45 also functions with Mdm38 to regulate translation of selected mitochondrial mRNAs, including Cox1 and cytochrome b [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 1996,\n      \"claim\": \"Established that MRPL45/Mba1 is a peripheral inner membrane protein needed for respiratory chain assembly, framing it as a biogenesis factor rather than a structural ribosomal component.\",\n      \"evidence\": \"Multicopy suppressor screen, gene disruption, c-myc tagging and subcellular fractionation in yeast\",\n      \"pmids\": [\"8690083\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not define molecular partners or the step in biogenesis affected\", \"Mode of membrane association characterized only operationally by extraction behavior\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Showed MRPL45 contacts mitochondrial translation products and nuclear-encoded conservatively sorted proteins during membrane integration, placing it in an Oxa1-independent insertion pathway and answering what process it serves.\",\n      \"evidence\": \"Co-IP/pulldown of translation products, double-mutant genetic analysis, import assays\",\n      \"pmids\": [\"11381092\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve whether interaction with ribosomes is direct or via nascent chains\", \"Substrate selectivity versus Oxa1 not fully delineated\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Defined the molecular role as a ribosome receptor binding the mitoribosome large subunit and cooperating with the Oxa1 C-terminus to align the exit tunnel with the insertion machinery.\",\n      \"evidence\": \"Ribosome-binding Co-IP, double-mutant analysis, Hsp70 substrate trapping in yeast\",\n      \"pmids\": [\"16601683\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of ribosome contact not resolved\", \"Functional redundancy with other receptors not yet identified\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Separated MRPL45's ribosome-tethering role from a distinct translation-regulatory function, showing that combined loss with Mdm38 mis-regulates Cox1 and cytochrome b mRNA translation independent of ribosome membrane binding.\",\n      \"evidence\": \"Double-mutant analysis, ribosome-membrane fractionation, mRNA chimera rescue experiments\",\n      \"pmids\": [\"20427570\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of mRNA-specific regulation unknown\", \"Whether MRPL45 binds the regulatory mRNA regions directly not established\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Connected MRPL45 to a specific maturation pathway by showing it stabilizes a Cox20-ribosome complex and escorts nascent Cox2 toward the Cox18 export machinery without entering the Cox20-Cox18 step.\",\n      \"evidence\": \"Co-IP, mass spectrometry, Cox18 genetic perturbation, ribosome-nascent chain pulldown\",\n      \"pmids\": [\"27550809\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Hand-off mechanism between insertion and Cox18 export not structurally defined\", \"Whether this role generalizes beyond Cox2 unclear\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Showed MRPL45 acts in parallel with the inner membrane protein Mrx15, both contacting the large ribosomal subunit via soluble C-terminal domains, establishing a redundant network organizing cotranslational membrane protein biogenesis.\",\n      \"evidence\": \"Systematic MS interaction screen, Co-IP, translation product cross-linking\",\n      \"pmids\": [\"30091672\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Division of labor between MRPL45 and Mrx15 across substrates not resolved\", \"Structural arrangement of the combined ribosome-membrane interface unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How MRPL45 mechanistically distinguishes its ribosome-tethering insertion function from its mRNA-selective translation-regulatory function, and the structural basis of its ribosome and membrane contacts, remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structure of MRPL45 on the mitoribosome at the insertion site\", \"Direct mRNA or regulatory-factor binding not demonstrated\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [2, 5]},\n      {\"term_id\": \"GO:0045182\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005743\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [1, 2, 4]},\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\n      \"mitochondrial large ribosomal subunit\",\n      \"Cox20-ribosome complex\"\n    ],\n    \"partners\": [\n      \"OXA1\",\n      \"MDM38\",\n      \"COX20\",\n      \"COX18\",\n      \"MRX15\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":6,"faith_total":6,"faith_pct":100.0}}