{"gene":"MRPL28","run_date":"2026-06-10T02:59:51","timeline":{"discoveries":[{"year":2009,"finding":"Knockdown of MRPL28 in pancreatic tumor cells decreased mitochondrial activity and increased glycolysis, but paradoxically decreased cellular growth in vitro while accelerating tumor growth in vivo, placing MRPL28 as a regulator of mitochondrial metabolism whose loss modulates oxygen consumption as a rate-limiting substrate for tumor proliferation.","method":"shRNA knockdown with in vitro growth assay and in vivo tumor growth measurement; oxygen consumption and glycolysis readouts","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean knockdown with defined cellular and in vivo phenotype, single lab, single gene-focused experiment within a broader screen","pmids":["19753307"],"is_preprint":false},{"year":2017,"finding":"The yeast ortholog MrpL28 (mL40) assembles into a mitoribosomal subcomplex together with MrpL35 (mL38), MrpL7 (uL5), Mrp7 (bL27), MrpL36 (bL31), and MrpL17 (mL46) as part of the mitoribosomal central protuberance, linking this subcomplex to coordination of Cox1 synthesis and cytochrome c oxidase (COX) assembly.","method":"Co-immunoprecipitation / subcomplex isolation in yeast; respiratory-defective mutant analysis; mitochondrial protein synthesis assay","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP defining subcomplex membership, combined with functional genetic analysis in yeast, single lab","pmids":["28931599"],"is_preprint":false}],"current_model":"MRPL28 (bL28m) is a structural component of the mitoribosomal large subunit that participates in a central-protuberance subcomplex involved in coordinating mitochondrial protein synthesis with oxidative phosphorylation assembly; its loss reduces mitochondrial activity and, in tumor cells, paradoxically alters the balance between oxidative phosphorylation and glycolysis to influence oxygen consumption and tumor growth."},"narrative":{"mechanistic_narrative":"MRPL28 (bL28m) is a structural component of the mitochondrial ribosomal large subunit that links mitochondrial protein synthesis to oxidative metabolism [PMID:19753307, PMID:28931599]. Its yeast ortholog MrpL28 (mL40) assembles into a central-protuberance subcomplex of the mitoribosome together with MrpL35, MrpL7, Mrp7, MrpL36, and MrpL17, a subcomplex that coordinates Cox1 synthesis with cytochrome c oxidase assembly [PMID:28931599]. Consistent with this role in sustaining the respiratory machinery, knockdown of MRPL28 in pancreatic tumor cells lowers mitochondrial activity and shifts metabolism toward glycolysis; this loss suppresses growth in vitro yet accelerates tumor growth in vivo, identifying MRPL28 as a modulator of oxygen consumption as a rate-limiting determinant of tumor proliferation [PMID:19753307]. Beyond these findings, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2009,"claim":"Established that MRPL28 is a functional regulator of mitochondrial metabolism whose loss rewires the balance between oxidative phosphorylation and glycolysis with opposing effects on cell growth and tumor growth.","evidence":"shRNA knockdown in pancreatic tumor cells with in vitro growth, in vivo tumor growth, oxygen consumption, and glycolysis readouts","pmids":["19753307"],"confidence":"Medium","gaps":["Did not define the molecular role of MRPL28 within the mitoribosome","Mechanism linking reduced mitochondrial activity to accelerated in vivo tumor growth not resolved","Single lab, single gene within a broader screen"]},{"year":2017,"claim":"Defined the structural and functional context of MRPL28 by placing its yeast ortholog in a mitoribosomal central-protuberance subcomplex coupling Cox1 synthesis to COX assembly.","evidence":"Co-immunoprecipitation/subcomplex isolation in yeast with respiratory-defective mutant analysis and mitochondrial protein synthesis assays","pmids":["28931599"],"confidence":"Medium","gaps":["Subcomplex membership and Cox1-coordination role shown in yeast, not confirmed in human mitoribosomes","Direct molecular mechanism by which the subcomplex coordinates translation with COX assembly not established","Connection between this structural role and the tumor metabolic phenotype not directly tested"]},{"year":null,"claim":"How the mitoribosomal structural role of MRPL28 mechanistically drives the metabolic and tumor-growth phenotypes in human cells remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No human mitoribosome subcomplex characterization in the corpus","No structural model of human MRPL28 in the timeline","Causal link between Cox1/COX coordination and the glycolytic shift untested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[1]}],"localization":[],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[1]},{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[0]}],"complexes":["mitochondrial large ribosomal subunit (central protuberance)"],"partners":["MRPL35","MRPL7","MRP7","MRPL36","MRPL17"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q13084","full_name":"Large ribosomal subunit protein bL28m","aliases":["39S ribosomal protein L28, mitochondrial","L28mt","MRP-L28","Melanoma antigen p15","Melanoma-associated antigen recognized by T-lymphocytes"],"length_aa":256,"mass_kda":30.2,"function":"","subcellular_location":"Mitochondrion","url":"https://www.uniprot.org/uniprotkb/Q13084/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/MRPL28","classification":"Common Essential","n_dependent_lines":675,"n_total_lines":1208,"dependency_fraction":0.5587748344370861},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/MRPL28","total_profiled":1310},"omim":[{"mim_id":"620646","title":"COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 59; COXPD59","url":"https://www.omim.org/entry/620646"},{"mim_id":"611845","title":"MITOCHONDRIAL RIBOSOMAL PROTEIN L39; MRPL39","url":"https://www.omim.org/entry/611845"},{"mim_id":"611838","title":"MITOCHONDRIAL RIBOSOMAL PROTEIN L30; MRPL30","url":"https://www.omim.org/entry/611838"},{"mim_id":"604853","title":"MITOCHONDRIAL RIBOSOMAL PROTEIN L28; MRPL28","url":"https://www.omim.org/entry/604853"}],"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/MRPL28"},"hgnc":{"alias_symbol":["p15","bL28m"],"prev_symbol":["MAAT1"]},"alphafold":{"accession":"Q13084","domains":[{"cath_id":"-","chopping":"37-42_51-209","consensus_level":"medium","plddt":94.8608,"start":37,"end":209}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q13084","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q13084-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q13084-F1-predicted_aligned_error_v6.png","plddt_mean":92.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MRPL28","jax_strain_url":"https://www.jax.org/strain/search?query=MRPL28"},"sequence":{"accession":"Q13084","fasta_url":"https://rest.uniprot.org/uniprotkb/Q13084.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q13084/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q13084"}},"corpus_meta":[{"pmid":"19753307","id":"PMC_19753307","title":"Oxygen consumption can regulate the growth of tumors, a new perspective on the Warburg effect.","date":"2009","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/19753307","citation_count":142,"is_preprint":false},{"pmid":"24166889","id":"PMC_24166889","title":"Differential DNA methylation profiles of infants exposed to maternal asthma during pregnancy.","date":"2013","source":"Pediatric pulmonology","url":"https://pubmed.ncbi.nlm.nih.gov/24166889","citation_count":56,"is_preprint":false},{"pmid":"33542190","id":"PMC_33542190","title":"DNA methylation differences associated with social anxiety disorder and early life adversity.","date":"2021","source":"Translational psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/33542190","citation_count":39,"is_preprint":false},{"pmid":"28931599","id":"PMC_28931599","title":"MrpL35, a mitospecific component of mitoribosomes, plays a key role in cytochrome c oxidase assembly.","date":"2017","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/28931599","citation_count":32,"is_preprint":false},{"pmid":"38086802","id":"PMC_38086802","title":"A novel microtubule inhibitor promotes tumor ferroptosis by attenuating SLC7A11/GPX4 signaling.","date":"2023","source":"Cell death discovery","url":"https://pubmed.ncbi.nlm.nih.gov/38086802","citation_count":20,"is_preprint":false},{"pmid":"23922663","id":"PMC_23922663","title":"QTL analysis of dietary obesity in C57BL/6byj X 129P3/J F2 mice: diet- and sex-dependent effects.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23922663","citation_count":17,"is_preprint":false},{"pmid":"12125055","id":"PMC_12125055","title":"Genomic differences between Candida glabrata and Saccharomyces cerevisiae around the MRPL28 and GCN3 loci.","date":"2002","source":"Yeast (Chichester, England)","url":"https://pubmed.ncbi.nlm.nih.gov/12125055","citation_count":6,"is_preprint":false},{"pmid":"37079096","id":"PMC_37079096","title":"Cryostress induces fragmentation and alters the abundance of sperm transcripts associated with fertilizing competence and reproductive processes in buffalo.","date":"2023","source":"Cell and tissue research","url":"https://pubmed.ncbi.nlm.nih.gov/37079096","citation_count":6,"is_preprint":false},{"pmid":"23089495","id":"PMC_23089495","title":"Characterization of TsMRP-L28, a mitochondrial ribosomal protein L28 from the parasitic nematode Trichinella spiralis.","date":"2012","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/23089495","citation_count":3,"is_preprint":false},{"pmid":"41899471","id":"PMC_41899471","title":"Effects of Hybridization and Triploidization on Transcription of Core Metabolic and Stress Response Genes in Rainbow Trout (Oncorhynchus mykiss) × Brook Trout (Salvelinus fontinalis) Hybrids-Preliminary Results.","date":"2026","source":"Current issues in molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/41899471","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7215,"output_tokens":606,"usd":0.015367,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6979,"output_tokens":1489,"usd":0.03606,"stage2_stop_reason":"end_turn"},"total_usd":0.051427,"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\": 2009,\n      \"finding\": \"Knockdown of MRPL28 in pancreatic tumor cells decreased mitochondrial activity and increased glycolysis, but paradoxically decreased cellular growth in vitro while accelerating tumor growth in vivo, placing MRPL28 as a regulator of mitochondrial metabolism whose loss modulates oxygen consumption as a rate-limiting substrate for tumor proliferation.\",\n      \"method\": \"shRNA knockdown with in vitro growth assay and in vivo tumor growth measurement; oxygen consumption and glycolysis readouts\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean knockdown with defined cellular and in vivo phenotype, single lab, single gene-focused experiment within a broader screen\",\n      \"pmids\": [\"19753307\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"The yeast ortholog MrpL28 (mL40) assembles into a mitoribosomal subcomplex together with MrpL35 (mL38), MrpL7 (uL5), Mrp7 (bL27), MrpL36 (bL31), and MrpL17 (mL46) as part of the mitoribosomal central protuberance, linking this subcomplex to coordination of Cox1 synthesis and cytochrome c oxidase (COX) assembly.\",\n      \"method\": \"Co-immunoprecipitation / subcomplex isolation in yeast; respiratory-defective mutant analysis; mitochondrial protein synthesis assay\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP defining subcomplex membership, combined with functional genetic analysis in yeast, single lab\",\n      \"pmids\": [\"28931599\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MRPL28 (bL28m) is a structural component of the mitoribosomal large subunit that participates in a central-protuberance subcomplex involved in coordinating mitochondrial protein synthesis with oxidative phosphorylation assembly; its loss reduces mitochondrial activity and, in tumor cells, paradoxically alters the balance between oxidative phosphorylation and glycolysis to influence oxygen consumption and tumor growth.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MRPL28 (bL28m) is a structural component of the mitochondrial ribosomal large subunit that links mitochondrial protein synthesis to oxidative metabolism [#0, #1]. Its yeast ortholog MrpL28 (mL40) assembles into a central-protuberance subcomplex of the mitoribosome together with MrpL35, MrpL7, Mrp7, MrpL36, and MrpL17, a subcomplex that coordinates Cox1 synthesis with cytochrome c oxidase assembly [#1]. Consistent with this role in sustaining the respiratory machinery, knockdown of MRPL28 in pancreatic tumor cells lowers mitochondrial activity and shifts metabolism toward glycolysis; this loss suppresses growth in vitro yet accelerates tumor growth in vivo, identifying MRPL28 as a modulator of oxygen consumption as a rate-limiting determinant of tumor proliferation [#0]. Beyond these findings, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Established that MRPL28 is a functional regulator of mitochondrial metabolism whose loss rewires the balance between oxidative phosphorylation and glycolysis with opposing effects on cell growth and tumor growth.\",\n      \"evidence\": \"shRNA knockdown in pancreatic tumor cells with in vitro growth, in vivo tumor growth, oxygen consumption, and glycolysis readouts\",\n      \"pmids\": [\"19753307\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Did not define the molecular role of MRPL28 within the mitoribosome\",\n        \"Mechanism linking reduced mitochondrial activity to accelerated in vivo tumor growth not resolved\",\n        \"Single lab, single gene within a broader screen\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Defined the structural and functional context of MRPL28 by placing its yeast ortholog in a mitoribosomal central-protuberance subcomplex coupling Cox1 synthesis to COX assembly.\",\n      \"evidence\": \"Co-immunoprecipitation/subcomplex isolation in yeast with respiratory-defective mutant analysis and mitochondrial protein synthesis assays\",\n      \"pmids\": [\"28931599\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Subcomplex membership and Cox1-coordination role shown in yeast, not confirmed in human mitoribosomes\",\n        \"Direct molecular mechanism by which the subcomplex coordinates translation with COX assembly not established\",\n        \"Connection between this structural role and the tumor metabolic phenotype not directly tested\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the mitoribosomal structural role of MRPL28 mechanistically drives the metabolic and tumor-growth phenotypes in human cells remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No human mitoribosome subcomplex characterization in the corpus\",\n        \"No structural model of human MRPL28 in the timeline\",\n        \"Causal link between Cox1/COX coordination and the glycolytic shift untested\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005761\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"mitochondrial large ribosomal subunit (central protuberance)\"\n    ],\n    \"partners\": [\n      \"MRPL35\",\n      \"MRPL7\",\n      \"MRP7\",\n      \"MRPL36\",\n      \"MRPL17\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":3,"faith_total":3,"faith_pct":100.0}}