{"gene":"MRPL17","run_date":"2026-06-10T02:59:51","timeline":{"discoveries":[{"year":2017,"finding":"MrpL17 (mL46) assembles into a subcomplex with MrpL35 (mL38), MrpL7 (uL5), Mrp7 (bL27), MrpL36 (bL31), and MrpL28 (mL40) within the yeast mitospecific central protuberance of the mitoribosome.","method":"Co-isolation/subcomplex purification of yeast mitoribosomal components","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — subcomplex co-isolation from a single lab; yeast ortholog (mL46) of human MRPL17 in defined mitoribosomal complex, single method","pmids":["28931599"],"is_preprint":false},{"year":2025,"finding":"MRPL17 silencing in NSCLC cells impaired mitochondrial respiratory function, causing reduced oxygen consumption, diminished Complex I activity, and decreased ATP production; these effects were partially reversible by antioxidant treatment or glucose supplementation. COX8A was identified as a direct downstream target of MRPL17, mediating its pro-cancerous effects.","method":"siRNA silencing and CRISPR knockout in NSCLC cell lines with oxygen consumption rate measurements, Complex I activity assays, ATP quantification, in vivo xenograft experiments, and bioinformatic/experimental confirmation of COX8A as downstream target","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal functional assays (KO/KD, metabolic measurements, in vivo) in single lab; COX8A downstream link confirmed experimentally","pmids":["41422086"],"is_preprint":false},{"year":2025,"finding":"siRNA-mediated FABP5 knockdown in decidual stromal cells triggered mitochondrial dysfunction and apoptosis mechanistically linked to MRPL17, described as a pivotal regulator of oxidative respiratory chain enzyme complex synthesis; MRPL17 overexpression alleviated the mitochondrial dysfunction and apoptosis caused by FABP5 deficiency.","method":"siRNA knockdown of FABP5, RNA-seq identification of MRPL17 as downstream target, MRPL17 overexpression rescue experiment, assessed by mitochondrial membrane potential (JC-1), COXIV immunostaining, ATP quantification, and apoptosis assays","journal":"Free radical biology & medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNA-seq target identification plus rescue experiment with MRPL17 overexpression, multiple functional readouts, single lab","pmids":["40480484"],"is_preprint":false},{"year":2026,"finding":"In a chronic social defeat stress mouse model of depression, Mrpl17 protein was differentially expressed in the prefrontal cortex, placing it in the mitochondrial function module; dysregulation was validated by parallel reaction monitoring (PRM) and Western blotting.","method":"Quantitative proteomics of prefrontal cortex, PPI network analysis, PRM and Western blot validation","journal":"Neuroscience letters","confidence":"Low","confidence_rationale":"Tier 3 / Weak — proteomics with validation confirms protein-level dysregulation but provides no direct mechanistic insight into MRPL17 function; single lab, single model","pmids":["41765126"],"is_preprint":false}],"current_model":"MRPL17 (bL17m/mL46) is a component of the mitoribosomal large subunit that assembles into a defined subcomplex at the central protuberance; it is required for mitochondrial respiratory chain function—specifically supporting Complex I activity, oxidative phosphorylation, and ATP production—and acts upstream of COX8A to sustain mitochondrial energetic output, with loss of MRPL17 causing mitochondrial dysfunction, oxidative stress, and apoptosis."},"narrative":{"mechanistic_narrative":"MRPL17 (bL17m/mL46) is a structural component of the mitochondrial ribosome large subunit that supports mitochondrial respiratory function and energetic output [PMID:28931599, PMID:41422086]. It assembles into a defined subcomplex at the mitospecific central protuberance of the mitoribosome together with mL38, uL5, bL27, bL31, and mL40 [PMID:28931599]. Functionally, MRPL17 is required to sustain oxidative phosphorylation: its loss reduces oxygen consumption, Complex I activity, and ATP production, with COX8A acting as a downstream effector mediating its pro-respiratory and pro-cancerous effects [PMID:41422086]. Consistent with this energetic role, MRPL17 acts as a regulator of respiratory chain function downstream of FABP5, and its overexpression rescues the mitochondrial dysfunction and apoptosis caused by FABP5 deficiency [PMID:40480484]. Beyond these roles in mitoribosome assembly and respiratory support, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2017,"claim":"Established that MRPL17/mL46 is not a free protein but an integral component of a defined mitoribosomal large-subunit subcomplex, localizing its function to the central protuberance of the mitoribosome.","evidence":"Co-isolation and subcomplex purification of yeast mitoribosomal components","pmids":["28931599"],"confidence":"Medium","gaps":["Single-lab co-isolation in yeast ortholog; assembly order and stoichiometry not resolved","No direct structural model of the human subcomplex","Role in human mitoribosome assembly not demonstrated"]},{"year":2025,"claim":"Demonstrated that MRPL17 is functionally required for respiratory chain output, linking its loss to reduced Complex I activity and ATP production, and identified COX8A as a direct downstream effector.","evidence":"siRNA/CRISPR knockout in NSCLC cell lines with oxygen consumption, Complex I activity, ATP assays, xenografts, and COX8A target confirmation","pmids":["41422086"],"confidence":"Medium","gaps":["Mechanism by which MRPL17 controls COX8A is not defined at the molecular level","Whether the respiratory defect reflects a general mitoribosome assembly failure versus a specific role is unresolved","Findings restricted to NSCLC context"]},{"year":2025,"claim":"Positioned MRPL17 as a downstream regulator of respiratory chain enzyme synthesis whose restoration can rescue mitochondrial dysfunction, showing its activity is rate-limiting for mitochondrial integrity in another cell type.","evidence":"siRNA FABP5 knockdown with RNA-seq, MRPL17 overexpression rescue, membrane potential, ATP, and apoptosis readouts in decidual stromal cells","pmids":["40480484"],"confidence":"Medium","gaps":["How FABP5 regulates MRPL17 expression mechanistically is unknown","Direct biochemical link between MRPL17 level and enzyme complex synthesis not shown","Single-lab rescue experiment"]},{"year":2026,"claim":"Associated MRPL17 protein dysregulation with a mitochondrial function module in a disease model, extending its relevance to in vivo pathophysiology without defining mechanism.","evidence":"Quantitative proteomics of prefrontal cortex with PRM and Western blot validation in a chronic social defeat stress mouse model","pmids":["41765126"],"confidence":"Low","gaps":["Correlative protein-level dysregulation only; no mechanistic insight into MRPL17 function","Causal contribution to the phenotype not tested","Single model, single lab"]},{"year":null,"claim":"The biochemical mechanism by which MRPL17 incorporation into the mitoribosome controls respiratory chain assembly and COX8A levels remains undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of the human MRPL17-containing subcomplex","Mechanism linking mitoribosome assembly to COX8A regulation unknown","No reconstitution of MRPL17 function in translation"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"GO:0005840","term_label":"ribosome","supporting_discovery_ids":[0]}],"complexes":["mitochondrial ribosome large subunit"],"partners":["MRPL35","MRPL7","MRPL36","MRPL28"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9NRX2","full_name":"Large ribosomal subunit protein bL17m","aliases":["39S ribosomal protein L17, mitochondrial","L17mt","MRP-L17","LYST-interacting protein 2"],"length_aa":175,"mass_kda":20.1,"function":"","subcellular_location":"Mitochondrion","url":"https://www.uniprot.org/uniprotkb/Q9NRX2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MRPL17","classification":"Not Classified","n_dependent_lines":659,"n_total_lines":1208,"dependency_fraction":0.5455298013245033},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/MRPL17","total_profiled":1310},"omim":[{"mim_id":"611830","title":"MITOCHONDRIAL RIBOSOMAL PROTEIN L17; MRPL17","url":"https://www.omim.org/entry/611830"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/MRPL17"},"hgnc":{"alias_symbol":["RPML26","MRP-L26","bL17m"],"prev_symbol":[]},"alphafold":{"accession":"Q9NRX2","domains":[{"cath_id":"3.90.1030.10","chopping":"6-126","consensus_level":"high","plddt":95.6479,"start":6,"end":126},{"cath_id":"1.20.5","chopping":"139-175","consensus_level":"medium","plddt":87.8916,"start":139,"end":175}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NRX2","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NRX2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NRX2-F1-predicted_aligned_error_v6.png","plddt_mean":93.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MRPL17","jax_strain_url":"https://www.jax.org/strain/search?query=MRPL17"},"sequence":{"accession":"Q9NRX2","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NRX2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NRX2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NRX2"}},"corpus_meta":[{"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":"35830453","id":"PMC_35830453","title":"Identification of the shared gene signatures and pathways between polycystic ovary syndrome and endometrial cancer: An omics data based combined approach.","date":"2022","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/35830453","citation_count":20,"is_preprint":false},{"pmid":"29236289","id":"PMC_29236289","title":"Assessment of cellular and serum proteome from tongue squamous cell carcinoma patient lacking addictive proclivities for tobacco, betel nut, and alcohol: Case study.","date":"2018","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/29236289","citation_count":13,"is_preprint":false},{"pmid":"36313967","id":"PMC_36313967","title":"Transcriptional profiles in olfactory pathway-associated brain regions of African green monkeys: Associations with age and Alzheimer's disease neuropathology.","date":"2022","source":"Alzheimer's & dementia (New York, N. Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/36313967","citation_count":8,"is_preprint":false},{"pmid":"31322542","id":"PMC_31322542","title":"Screening of key genes and prediction of therapeutic agents in Arsenic-induced lung carcinoma.","date":"2019","source":"Cancer biomarkers : section A of Disease markers","url":"https://pubmed.ncbi.nlm.nih.gov/31322542","citation_count":7,"is_preprint":false},{"pmid":"39933430","id":"PMC_39933430","title":"Mitochondrial-related genome-wide Mendelian randomization identifies putatively causal genes in the pathogenesis of sepsis.","date":"2025","source":"Surgery","url":"https://pubmed.ncbi.nlm.nih.gov/39933430","citation_count":5,"is_preprint":false},{"pmid":"40410506","id":"PMC_40410506","title":"Father's adolescent body silhouette is associated with offspring asthma, lung function and BMI through DNA methylation.","date":"2025","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/40410506","citation_count":3,"is_preprint":false},{"pmid":"40480484","id":"PMC_40480484","title":"Oxidative stress-induced decreased expression of FABP5 leads to mitochondrial damage and survival disorder of decidual stromal cells in women with recurrent spontaneous abortion.","date":"2025","source":"Free radical biology & medicine","url":"https://pubmed.ncbi.nlm.nih.gov/40480484","citation_count":1,"is_preprint":false},{"pmid":"39814280","id":"PMC_39814280","title":"Identification and validation of Atp5f1c in CD4+ T cell as a hub protein in Parkinson's disease.","date":"2025","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/39814280","citation_count":1,"is_preprint":false},{"pmid":"41422086","id":"PMC_41422086","title":"MRPL17 is a critical regulator of mitochondrial function and a novel therapeutic target in non-small cell lung cancer.","date":"2025","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/41422086","citation_count":0,"is_preprint":false},{"pmid":"41851356","id":"PMC_41851356","title":"A distinct tau oligomer strain defines the molecular and proteomic landscape of rapidly progressive Alzheimer's disease.","date":"2026","source":"Acta neuropathologica","url":"https://pubmed.ncbi.nlm.nih.gov/41851356","citation_count":0,"is_preprint":false},{"pmid":"41765126","id":"PMC_41765126","title":"Proteomic profiling of the prefrontal cortex reveals Dysregulated Mitochondria-Metabolism-Synapse axis in a chronic Stress-Induced mouse model of depression.","date":"2026","source":"Neuroscience letters","url":"https://pubmed.ncbi.nlm.nih.gov/41765126","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8856,"output_tokens":1100,"usd":0.021534,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7694,"output_tokens":1918,"usd":0.04321,"stage2_stop_reason":"end_turn"},"total_usd":0.064744,"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\": 2017,\n      \"finding\": \"MrpL17 (mL46) assembles into a subcomplex with MrpL35 (mL38), MrpL7 (uL5), Mrp7 (bL27), MrpL36 (bL31), and MrpL28 (mL40) within the yeast mitospecific central protuberance of the mitoribosome.\",\n      \"method\": \"Co-isolation/subcomplex purification of yeast mitoribosomal components\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — subcomplex co-isolation from a single lab; yeast ortholog (mL46) of human MRPL17 in defined mitoribosomal complex, single method\",\n      \"pmids\": [\"28931599\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"MRPL17 silencing in NSCLC cells impaired mitochondrial respiratory function, causing reduced oxygen consumption, diminished Complex I activity, and decreased ATP production; these effects were partially reversible by antioxidant treatment or glucose supplementation. COX8A was identified as a direct downstream target of MRPL17, mediating its pro-cancerous effects.\",\n      \"method\": \"siRNA silencing and CRISPR knockout in NSCLC cell lines with oxygen consumption rate measurements, Complex I activity assays, ATP quantification, in vivo xenograft experiments, and bioinformatic/experimental confirmation of COX8A as downstream target\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal functional assays (KO/KD, metabolic measurements, in vivo) in single lab; COX8A downstream link confirmed experimentally\",\n      \"pmids\": [\"41422086\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"siRNA-mediated FABP5 knockdown in decidual stromal cells triggered mitochondrial dysfunction and apoptosis mechanistically linked to MRPL17, described as a pivotal regulator of oxidative respiratory chain enzyme complex synthesis; MRPL17 overexpression alleviated the mitochondrial dysfunction and apoptosis caused by FABP5 deficiency.\",\n      \"method\": \"siRNA knockdown of FABP5, RNA-seq identification of MRPL17 as downstream target, MRPL17 overexpression rescue experiment, assessed by mitochondrial membrane potential (JC-1), COXIV immunostaining, ATP quantification, and apoptosis assays\",\n      \"journal\": \"Free radical biology & medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNA-seq target identification plus rescue experiment with MRPL17 overexpression, multiple functional readouts, single lab\",\n      \"pmids\": [\"40480484\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"In a chronic social defeat stress mouse model of depression, Mrpl17 protein was differentially expressed in the prefrontal cortex, placing it in the mitochondrial function module; dysregulation was validated by parallel reaction monitoring (PRM) and Western blotting.\",\n      \"method\": \"Quantitative proteomics of prefrontal cortex, PPI network analysis, PRM and Western blot validation\",\n      \"journal\": \"Neuroscience letters\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — proteomics with validation confirms protein-level dysregulation but provides no direct mechanistic insight into MRPL17 function; single lab, single model\",\n      \"pmids\": [\"41765126\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MRPL17 (bL17m/mL46) is a component of the mitoribosomal large subunit that assembles into a defined subcomplex at the central protuberance; it is required for mitochondrial respiratory chain function—specifically supporting Complex I activity, oxidative phosphorylation, and ATP production—and acts upstream of COX8A to sustain mitochondrial energetic output, with loss of MRPL17 causing mitochondrial dysfunction, oxidative stress, and apoptosis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MRPL17 (bL17m/mL46) is a structural component of the mitochondrial ribosome large subunit that supports mitochondrial respiratory function and energetic output [#0, #1]. It assembles into a defined subcomplex at the mitospecific central protuberance of the mitoribosome together with mL38, uL5, bL27, bL31, and mL40 [#0]. Functionally, MRPL17 is required to sustain oxidative phosphorylation: its loss reduces oxygen consumption, Complex I activity, and ATP production, with COX8A acting as a downstream effector mediating its pro-respiratory and pro-cancerous effects [#1]. Consistent with this energetic role, MRPL17 acts as a regulator of respiratory chain function downstream of FABP5, and its overexpression rescues the mitochondrial dysfunction and apoptosis caused by FABP5 deficiency [#2]. Beyond these roles in mitoribosome assembly and respiratory support, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Established that MRPL17/mL46 is not a free protein but an integral component of a defined mitoribosomal large-subunit subcomplex, localizing its function to the central protuberance of the mitoribosome.\",\n      \"evidence\": \"Co-isolation and subcomplex purification of yeast mitoribosomal components\",\n      \"pmids\": [\"28931599\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Single-lab co-isolation in yeast ortholog; assembly order and stoichiometry not resolved\",\n        \"No direct structural model of the human subcomplex\",\n        \"Role in human mitoribosome assembly not demonstrated\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstrated that MRPL17 is functionally required for respiratory chain output, linking its loss to reduced Complex I activity and ATP production, and identified COX8A as a direct downstream effector.\",\n      \"evidence\": \"siRNA/CRISPR knockout in NSCLC cell lines with oxygen consumption, Complex I activity, ATP assays, xenografts, and COX8A target confirmation\",\n      \"pmids\": [\"41422086\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Mechanism by which MRPL17 controls COX8A is not defined at the molecular level\",\n        \"Whether the respiratory defect reflects a general mitoribosome assembly failure versus a specific role is unresolved\",\n        \"Findings restricted to NSCLC context\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Positioned MRPL17 as a downstream regulator of respiratory chain enzyme synthesis whose restoration can rescue mitochondrial dysfunction, showing its activity is rate-limiting for mitochondrial integrity in another cell type.\",\n      \"evidence\": \"siRNA FABP5 knockdown with RNA-seq, MRPL17 overexpression rescue, membrane potential, ATP, and apoptosis readouts in decidual stromal cells\",\n      \"pmids\": [\"40480484\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"How FABP5 regulates MRPL17 expression mechanistically is unknown\",\n        \"Direct biochemical link between MRPL17 level and enzyme complex synthesis not shown\",\n        \"Single-lab rescue experiment\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Associated MRPL17 protein dysregulation with a mitochondrial function module in a disease model, extending its relevance to in vivo pathophysiology without defining mechanism.\",\n      \"evidence\": \"Quantitative proteomics of prefrontal cortex with PRM and Western blot validation in a chronic social defeat stress mouse model\",\n      \"pmids\": [\"41765126\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Correlative protein-level dysregulation only; no mechanistic insight into MRPL17 function\",\n        \"Causal contribution to the phenotype not tested\",\n        \"Single model, single lab\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical mechanism by which MRPL17 incorporation into the mitoribosome controls respiratory chain assembly and COX8A levels remains undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No structural model of the human MRPL17-containing subcomplex\",\n        \"Mechanism linking mitoribosome assembly to COX8A regulation unknown\",\n        \"No reconstitution of MRPL17 function in translation\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0005840\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"mitochondrial ribosome large subunit\"],\n    \"partners\": [\"MRPL35\", \"MRPL7\", \"MRPL36\", \"MRPL28\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":3,"faith_total":4,"faith_pct":75.0}}