{"gene":"OXA1L","run_date":"2026-04-29T11:37:57","timeline":{"discoveries":[{"year":1994,"finding":"The yeast OXA1 nuclear gene product is required post-translationally for cytochrome c oxidase biogenesis and assembly; null mutations abolish cytochrome aa3 and reduce cytochrome b, with mitochondrially encoded COX subunits still synthesized but assembly impaired.","method":"Genetic analysis, cytochrome spectra, gene disruption (oxa1::LEU2)","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 2 — clean KO with defined biochemical phenotype, replicated by complementation and disruption alleles","pmids":["8196054"],"is_preprint":false},{"year":1994,"finding":"A human OXA1L cDNA functionally complements yeast oxa1 mutants and restores cytochrome oxidase assembly, demonstrating conserved function between yeast Oxa1 and human OXA1L.","method":"Genetic complementation, oxygen consumption measurements, cytochrome absorption spectra","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 — functional rescue across species with multiple biochemical readouts","pmids":["7991568"],"is_preprint":false},{"year":1996,"finding":"Yeast Oxa1p is required for correct assembly of both cytochrome c oxidase and oligomycin-sensitive ATP synthase, as shown by absence of heme aa3, loss of cytochrome c oxidoreductase activity, and dramatic decrease of oligomycin-sensitive ATPase in deletion strains.","method":"Cytochrome spectra, enzymatic activity measurements, non-denaturing PAGE analysis of respiratory complexes","journal":"FEBS letters","confidence":"High","confidence_rationale":"Tier 2 — KO with multiple orthogonal biochemical readouts","pmids":["8612730"],"is_preprint":false},{"year":2002,"finding":"Oxa1 forms a homooligomeric complex of ~170-180 kDa (likely a tetramer) in the Neurospora crassa mitochondrial inner membrane and is an essential component of the OXA translocase.","method":"Native complex isolation, biochemical fractionation, molecular weight analysis","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 — single lab, direct biochemical isolation of complex","pmids":["11823466"],"is_preprint":false},{"year":2003,"finding":"The matrix-exposed C-terminus of yeast Oxa1 forms an alpha-helical domain that binds to mitochondrial ribosomes (large subunit), and deletion of this domain strongly reduces co-translational membrane insertion efficiency of mitochondrially encoded Cox2.","method":"Ribosome binding assays, deletion analysis, import and insertion assays","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 — reciprocal binding assays plus functional deletion phenotype, independently replicated (PMID 14657017 and 14657018)","pmids":["14657018","14657017"],"is_preprint":false},{"year":2003,"finding":"Yeast Oxa1 physically associates with the large mitochondrial ribosomal subunit; the C-terminal region mediates this interaction, and Oxa1 can be crosslinked to Mrp20 (homolog of bacterial L23, located near the peptide exit tunnel).","method":"Co-sedimentation, chemical crosslinking, reciprocal Co-IP","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (crosslinking + co-sedimentation), replicated in two simultaneous publications","pmids":["14657017","14657018"],"is_preprint":false},{"year":2003,"finding":"The dependence of protein domains on the Oxa1 translocase for export across the mitochondrial inner membrane correlates with the net charge of the translocated domain, not its position in the sequence.","method":"Genetic and biochemical analysis using fusion proteins in yeast mitochondria","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 — genetic epistasis combined with biochemical insertion assays","pmids":["14593095"],"is_preprint":false},{"year":2007,"finding":"Yeast Oxa1 directly and physically interacts with newly synthesized mitochondrially encoded Atp9 (F1Fo-ATP synthase subunit c) in a posttranslational manner, and is required for the assembly of the Atp9-F1 subcomplex with subunit Atp6; this interaction does not require the C-terminal matrix region of Oxa1.","method":"Co-immunoprecipitation, pulse-chase analysis, blue native PAGE","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — direct Co-IP with pulse-chase plus assembly analysis by BN-PAGE","pmids":["17344477"],"is_preprint":false},{"year":2007,"finding":"Human OXA1L (42 kDa) localizes exclusively to mitochondria as an integral inner membrane protein and is part of a 600-700 kDa complex; shRNA-mediated knockdown reduces F1Fo-ATP synthase steady-state levels and activity and moderately reduces complex I, but does not affect cytochrome c oxidase (complex IV) or cytochrome bc1 (complex III).","method":"shRNA knockdown, 2D BN/denaturing PAGE, ATPase activity assay, fractionation, FLAG-tagging and immunolocalization","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 2 — stable KD with multiple orthogonal biochemical readouts","pmids":["17936786"],"is_preprint":false},{"year":2009,"finding":"Cryo-EM structures of yeast Oxa1 bound to E. coli ribosome nascent-chain complexes show that Oxa1 forms dimers positioned above the ribosomal tunnel exit; conserved transmembrane helices localize to the dimer interface; Oxa1 contacts ribosomal protein L23 and conserved rRNA helices H59 and H24.","method":"Cryo-electron microscopy, cysteine crosslinking","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1 — cryo-EM structure with crosslinking validation","pmids":["19450532"],"is_preprint":false},{"year":2009,"finding":"The C-terminal tail of human Oxa1L (Oxa1L-CTT) binds to mammalian mitochondrial ribosomes with a Kd of 0.3-0.8 µM and a stoichiometry of 2; it crosslinks to mammalian mitochondrial homologs of ribosomal proteins L13, L20, L28, and mitochondria-specific proteins MRPL48, MRPL49, and MRPL51 — a binding interface distinct from the conventional peptide exit tunnel.","method":"Fluorescence binding assays, chemical crosslinking, mass spectrometry","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1-2 — quantitative binding analysis plus crosslinking with protein identification","pmids":["20601428"],"is_preprint":false},{"year":2009,"finding":"Mammalian Oxa1 has five transmembrane segments and adopts an N-out (IMS), C-in (matrix) topology; a conserved hexapeptide (GLPWWG) near TM1 is essential for correct topogenesis including export of the N-terminal segment to the IMS; all five TMs cooperatively mediate membrane integration.","method":"Systematic deletion/mutation constructs in HeLa cells, protease protection assays, alkaline extraction","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — systematic mutagenesis with functional topology mapping","pmids":["19349278"],"is_preprint":false},{"year":2009,"finding":"During its own biogenesis, Oxa1 initially accumulates at Tim23 (the inner membrane protein translocase) and requires mtHsp70 for presequence cleavage, but membrane insertion of the mature protein is mtHsp70-independent, indicating Oxa1 accepts preproteins within the membrane from Tim23.","method":"Import assays in yeast mitochondria, co-immunoprecipitation with Tim23, use of mtHsp70 mutants","journal":"Journal of molecular biology","confidence":"Medium","confidence_rationale":"Tier 2 — import assays with defined mutants and co-IP, single lab","pmids":["16253275"],"is_preprint":false},{"year":2010,"finding":"The C-terminal tail of human Oxa1L (Oxa1L-CTT) does not form a stable coiled-coil in solution (contrary to yeast), but forms oligomers cooperatively in a submicromolar range; contacts near a long helix around position 39 mediate oligomer formation; the tail undergoes conformational changes and induced oligomerization upon ribosome binding.","method":"Fluorescence anisotropy, fluorescence lifetime measurements, fluorescence correlation spectroscopy","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 — biophysical characterization with multiple fluorescence methods, single lab","pmids":["20739282"],"is_preprint":false},{"year":2012,"finding":"Purified and reconstituted yeast Oxa1 forms a cation-selective protein-conducting channel that specifically responds to mitochondrial export signals; single-channel analysis revealed four discrete channels per active unit, suggesting a tetrameric pore with a restriction zone diameter of 0.6-2 nm sufficient for polypeptide translocation.","method":"Protein purification, reconstitution into lipid bilayers, electrophysiology/single-channel analysis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 — in vitro reconstitution with electrophysiology and functional characterization","pmids":["22829595"],"is_preprint":false},{"year":2012,"finding":"Insertion of flexible linkers between the Oxa1 insertase domain and ribosome-binding region causes length-dependent defects in cytochrome c oxidase assembly (not just membrane insertion), demonstrating that close proximity of Oxa1 to ribosomes is critical for productive assembly coordination of COX subunits.","method":"Yeast genetics, linker insertion mutagenesis, respiratory activity measurements, immunoblotting","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 — systematic mutagenesis with functional readout, single lab","pmids":["22904327"],"is_preprint":false},{"year":2012,"finding":"Oxa1 is required for efficient import and biogenesis of mitochondrial carrier proteins (including Aac2/ATP-ADP carrier), which are inserted from the IMS side and lack bacterial homologs, expanding the known substrate spectrum of Oxa1 beyond conserved endosymbiotic proteins.","method":"Temperature-sensitive oxa1 mutant, in vitro import assays, steady-state level analysis","journal":"Journal of molecular biology","confidence":"Medium","confidence_rationale":"Tier 2 — novel temperature-sensitive mutant with in vitro import assays, single lab","pmids":["22846909"],"is_preprint":false},{"year":2012,"finding":"Yeast Oxa1 distribution between the inner boundary membrane (IBM) and cristae membrane (CM) is dynamic: enriched in IBM under fermentable conditions (driven by nuclear-encoded substrate import) and in CM under respiratory conditions (requiring both mitochondrial translation and the ribosome-binding domain of Oxa1).","method":"STED superresolution microscopy, fractionation, genetic deletion of ribosome-binding domain","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 — direct superresolution imaging combined with genetic manipulations","pmids":["22513091"],"is_preprint":false},{"year":2018,"finding":"Human OXA1L is required for the assembly of multiple respiratory chain complexes (I, IV, and V); immunoprecipitation of OXA1L enriches mtDNA-encoded subunits of complexes I, IV, and V; expression of wild-type OXA1L in patient fibroblasts with biallelic OXA1L variants rescues complex IV and V defects.","method":"Whole exome sequencing, patient cell complementation, targeted OXA1L depletion in human cells and Drosophila, immunoprecipitation-mass spectrometry, BN-PAGE","journal":"EMBO molecular medicine","confidence":"High","confidence_rationale":"Tier 2 — patient variant functional validation by complementation, Co-IP/MS, and multiple model systems","pmids":["30201738"],"is_preprint":false},{"year":2023,"finding":"NMR analysis of yeast Oxa1-CTD reveals it forms a transient α-helical structure within residues P342-Q385; two conserved ribosome contact sites were identified: a N-terminal site (V321-I327) and a central stretch (I348-Q370) that transitions from transient to stable helix upon ribosome binding.","method":"NMR spectroscopy, chemical shift perturbation analysis with E. coli 70S ribosomes","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 1-2 — NMR structural characterization with ribosome interaction mapping, single lab","pmids":["37834108"],"is_preprint":false},{"year":2024,"finding":"TMEM126A is a physical interactor of human OXA1L; TMEM126A associates with mitochondrial ribosomes and translation products and cooperates with OXA1L in cotranslational protein insertion into the inner membrane; loss of TMEM126A destabilizes mitochondrial translation products, which together with cargo-blocked OXA1L are degraded by the mitochondrial iAAA protease.","method":"Co-immunoprecipitation, proximity labeling, ribosome association assays, iAAA protease degradation assays","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP plus functional characterization with protease degradation pathway, multiple orthogonal methods","pmids":["38199007"],"is_preprint":false},{"year":2025,"finding":"OXA1L deficiency in skeletal muscle cells causes combined mitochondrial respiratory chain defects and OXPHOS impairments; elevated ROS production resulting from OXPHOS dysfunction activates the NF-κB signalling pathway, triggering apoptosis; wild-type but not truncated mutant OXA1L rescues respiratory chain defects in KO cells.","method":"hiPSC differentiation, CRISPR/Cas9 KO, conditional skeletal muscle KO mouse model, complementation with WT vs mutant OXA1L","journal":"Clinical and translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 — multiple model systems with complementation controls, single lab","pmids":["40551575"],"is_preprint":false}],"current_model":"OXA1L (human) / Oxa1 (yeast) is a conserved integral inner mitochondrial membrane insertase that co-translationally inserts mtDNA-encoded subunits of respiratory chain complexes I, IV, and V into the inner membrane by forming a homo-oligomeric, cation-selective protein-conducting channel; its matrix-exposed C-terminal tail directly binds the large mitochondrial ribosomal subunit (via specific ribosomal proteins distinct from the canonical exit-tunnel contacts) to couple translation with membrane insertion, and it additionally cooperates with the newly identified partner TMEM126A for cotranslational quality control, with cargo-blocked OXA1L complexes cleared by the iAAA protease."},"narrative":{"teleology":[{"year":1994,"claim":"Establishing OXA1L as a conserved mitochondrial assembly factor: yeast Oxa1 was shown to be required for cytochrome c oxidase biogenesis, and human OXA1L cDNA functionally rescued the yeast null mutant, demonstrating deep functional conservation of a membrane protein insertase.","evidence":"Gene disruption in yeast with cytochrome spectra and respiratory measurements; cross-species complementation of yeast oxa1Δ by human OXA1L","pmids":["8196054","7991568"],"confidence":"High","gaps":["Substrate range beyond complex IV not yet defined","Mechanism of insertion (channel vs chaperone) unknown","Topology of Oxa1 in the membrane not determined"]},{"year":1996,"claim":"The substrate repertoire was expanded beyond complex IV: Oxa1 was also required for oligomycin-sensitive ATP synthase assembly, establishing it as a general insertase for multiple OXPHOS complexes.","evidence":"Enzymatic activity measurements and BN-PAGE of respiratory complexes in yeast oxa1Δ","pmids":["8612730"],"confidence":"High","gaps":["Whether complex I (absent in yeast) is also a substrate remained unknown","Whether Oxa1 acts co- or post-translationally not resolved"]},{"year":2003,"claim":"The mechanism coupling translation to insertion was revealed: the C-terminal matrix tail of Oxa1 binds the large mitochondrial ribosomal subunit near the peptide exit tunnel, and this interaction is required for efficient co-translational membrane insertion.","evidence":"Ribosome co-sedimentation, chemical crosslinking to Mrp20/L23, deletion analysis with Cox2 insertion assays in yeast","pmids":["14657018","14657017"],"confidence":"High","gaps":["Binding interface on mammalian mitoribosome not yet mapped","Structural basis of the Oxa1-ribosome interaction unknown","Whether oligomerization is functionally linked to ribosome binding unclear"]},{"year":2007,"claim":"OXA1L function was characterized in mammalian cells: human OXA1L resides in a ~600-700 kDa inner membrane complex, and its depletion primarily reduces ATP synthase and complex I levels, revealing a partially distinct substrate hierarchy compared to yeast.","evidence":"shRNA knockdown in human cells with 2D BN/SDS-PAGE, ATPase activity assays, and FLAG-tag immunolocalization","pmids":["17936786"],"confidence":"High","gaps":["Why complex IV was unaffected in human KD (unlike yeast) not explained","Identity of co-complex partners in the 600-700 kDa assembly unknown"]},{"year":2009,"claim":"Structural and biophysical work defined the insertase architecture and its ribosome-binding mode: cryo-EM showed Oxa1 dimers docked above the ribosomal exit tunnel; the human OXA1L C-terminal tail binds mitoribosomes at a site involving L13, L20, L28, MRPL48, MRPL49, and MRPL51—distinct from the canonical exit tunnel contacts; and mammalian Oxa1L was shown to have five transmembrane segments with N-out/C-in topology.","evidence":"Cryo-EM of Oxa1-ribosome complexes, fluorescence binding assays with Kd measurement, crosslinking-MS, systematic deletion/topology mapping in HeLa cells","pmids":["19450532","20601428","19349278"],"confidence":"High","gaps":["High-resolution structure of the transmembrane channel not available","Whether the mammalian binding interface functions identically to the yeast one not tested in vivo"]},{"year":2012,"claim":"The protein-conducting channel was reconstituted and characterized: Oxa1 forms a cation-selective channel with four discrete conductance states responsive to mitochondrial export signals, consistent with a tetrameric pore; close proximity of the insertase to ribosomes was shown to be critical not just for insertion but for downstream assembly of COX subunits.","evidence":"Reconstitution into lipid bilayers with single-channel electrophysiology; linker-insertion mutagenesis with respiratory function assays in yeast","pmids":["22829595","22904327"],"confidence":"High","gaps":["Pore structure at atomic resolution not determined","How the channel discriminates substrates from non-substrates mechanistically unclear"]},{"year":2018,"claim":"Clinical relevance and full human substrate spectrum were established: biallelic OXA1L variants cause combined OXPHOS deficiency with severe encephalopathy; OXA1L physically associates with mtDNA-encoded subunits of complexes I, IV, and V, and wild-type OXA1L rescues patient cell defects.","evidence":"Whole-exome sequencing of patients, complementation in patient fibroblasts, IP-MS, and Drosophila OXA1L depletion","pmids":["30201738"],"confidence":"High","gaps":["Genotype-phenotype correlations across different OXA1L mutations not established","Whether partial loss of function produces tissue-specific phenotypes not explored"]},{"year":2024,"claim":"A cotranslational quality-control pathway was uncovered: TMEM126A was identified as a physical partner of OXA1L that cooperates in cotranslational insertion; when TMEM126A is lost, translation products are destabilized and cargo-blocked OXA1L complexes are degraded by the iAAA protease.","evidence":"Reciprocal co-immunoprecipitation, proximity labeling, ribosome association assays, iAAA protease degradation assays in human cells","pmids":["38199007"],"confidence":"High","gaps":["Structural basis of OXA1L-TMEM126A interaction not resolved","Whether iAAA-mediated clearance is a general surveillance mechanism for all insertase substrates unknown"]},{"year":2025,"claim":"Downstream pathological consequences of OXA1L loss were delineated in muscle: OXA1L deficiency causes OXPHOS impairment leading to elevated ROS, NF-κB activation, and apoptosis in skeletal muscle.","evidence":"hiPSC-derived skeletal muscle cells, CRISPR KO, conditional muscle KO mouse, complementation with WT vs truncated mutant","pmids":["40551575"],"confidence":"Medium","gaps":["Whether NF-κB activation is a direct ROS effect or involves intermediate signaling not resolved","Tissue-specific vulnerability across different OXA1L mutations not systematically compared"]},{"year":null,"claim":"A high-resolution structure of the OXA1L transmembrane channel in complex with a nascent chain and the human mitoribosome is still lacking, which would clarify substrate recognition, the mechanism of lateral release into the lipid bilayer, and functional coordination with TMEM126A.","evidence":"","pmids":[],"confidence":"High","gaps":["No atomic-resolution structure of the human OXA1L channel","Mechanism of lateral gate opening for substrate release into lipid bilayer unknown","How OXA1L distinguishes co- from post-translational substrates mechanistically unresolved"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005215","term_label":"transporter activity","supporting_discovery_ids":[14,6,11]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,2,8,18]}],"localization":[{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[8,11,17]}],"pathway":[{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[0,2,8,18]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[4,5,10,20]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[8,17,18]}],"complexes":["OXA1L homo-oligomeric insertase complex","OXA1L-TMEM126A cotranslational insertion complex"],"partners":["TMEM126A","MRPL13","MRPL20","MRPL28","MRPL48","MRPL49","MRPL51"],"other_free_text":[]},"mechanistic_narrative":"OXA1L is a conserved integral inner mitochondrial membrane insertase that co-translationally inserts mtDNA-encoded subunits of oxidative phosphorylation complexes I, IV, and V into the inner membrane [PMID:8196054, PMID:7991568, PMID:30201738]. It forms a homo-oligomeric, cation-selective protein-conducting channel with four discrete pores sufficient for polypeptide translocation, and its matrix-exposed C-terminal tail directly binds the large mitochondrial ribosomal subunit—contacting ribosomal proteins distinct from the canonical peptide exit tunnel in mammals—to couple translation with membrane insertion [PMID:22829595, PMID:20601428, PMID:14657018]. OXA1L cooperates with TMEM126A for cotranslational quality control, and cargo-blocked OXA1L complexes are cleared by the mitochondrial iAAA protease [PMID:38199007]. Biallelic loss-of-function variants in OXA1L cause combined OXPHOS deficiency with severe encephalopathy, and OXA1L deficiency in skeletal muscle triggers ROS-mediated NF-κB activation and apoptosis [PMID:30201738, PMID:40551575]."},"prefetch_data":{"uniprot":{"accession":"Q15070","full_name":"Mitochondrial inner membrane protein OXA1L","aliases":["OXA1Hs","Oxidase assembly 1-like protein","OXA1-like protein"],"length_aa":435,"mass_kda":48.5,"function":"Mitochondrial membrane insertase that mediates the cotranslational insertion of integral membrane proteins into the mitochondrial inner membrane (PubMed:17936786, PubMed:33602856, PubMed:7991568). Essential for the activity and assembly of cytochrome oxidase (PubMed:17936786, PubMed:7991568). Required for the correct biogenesis of ATP synthase and complex I in mitochondria (PubMed:17936786, PubMed:7991568)","subcellular_location":"Mitochondrion inner membrane","url":"https://www.uniprot.org/uniprotkb/Q15070/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/OXA1L","classification":"Common Essential","n_dependent_lines":757,"n_total_lines":1208,"dependency_fraction":0.6266556291390728},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/OXA1L","total_profiled":1310},"omim":[{"mim_id":"618583","title":"MITOCHONDRIAL TRANSCRIPTION RESCUE FACTOR 1; MTRES1","url":"https://www.omim.org/entry/618583"},{"mim_id":"617228","title":"COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 31; COXPD31","url":"https://www.omim.org/entry/617228"},{"mim_id":"613541","title":"MITOCHONDRIAL TRANSLATION RELEASE FACTOR IN RESCUE; MTRFR","url":"https://www.omim.org/entry/613541"},{"mim_id":"610428","title":"CYTOCHROME c OXIDASE ASSEMBLY FACTOR COX18; COX18","url":"https://www.omim.org/entry/610428"},{"mim_id":"602241","title":"MITOCHONDRIAL INTERMEDIATE PEPTIDASE; MIPEP","url":"https://www.omim.org/entry/602241"}],"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/OXA1L"},"hgnc":{"alias_symbol":["MGC133129","OXA1","OXA1L1"],"prev_symbol":[]},"alphafold":{"accession":"Q15070","domains":[{"cath_id":"-","chopping":"107-355","consensus_level":"high","plddt":87.661,"start":107,"end":355},{"cath_id":"1.20.5","chopping":"362-386","consensus_level":"medium","plddt":86.9368,"start":362,"end":386}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15070","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q15070-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q15070-F1-predicted_aligned_error_v6.png","plddt_mean":73.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=OXA1L","jax_strain_url":"https://www.jax.org/strain/search?query=OXA1L"},"sequence":{"accession":"Q15070","fasta_url":"https://rest.uniprot.org/uniprotkb/Q15070.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q15070/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15070"}},"corpus_meta":[{"pmid":"11731127","id":"PMC_11731127","title":"Phylogenetic and structural analyses of the oxa1 family of protein translocases.","date":"2001","source":"FEMS microbiology letters","url":"https://pubmed.ncbi.nlm.nih.gov/11731127","citation_count":274,"is_preprint":false},{"pmid":"14657018","id":"PMC_14657018","title":"Ribosome binding to the Oxa1 complex facilitates co-translational protein insertion in mitochondria.","date":"2003","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/14657018","citation_count":205,"is_preprint":false},{"pmid":"2823258","id":"PMC_2823258","title":"Precise insertion of antibiotic resistance determinants into Tn21-like transposons: nucleotide sequence of the OXA-1 beta-lactamase gene.","date":"1987","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/2823258","citation_count":202,"is_preprint":false},{"pmid":"8196054","id":"PMC_8196054","title":"OXA1, a Saccharomyces cerevisiae nuclear gene whose sequence is conserved from prokaryotes to eukaryotes controls cytochrome oxidase biogenesis.","date":"1994","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/8196054","citation_count":184,"is_preprint":false},{"pmid":"14657017","id":"PMC_14657017","title":"Yeast Oxa1 interacts with mitochondrial ribosomes: the importance of the C-terminal region of Oxa1.","date":"2003","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/14657017","citation_count":178,"is_preprint":false},{"pmid":"8612730","id":"PMC_8612730","title":"The Saccharomyces cerevisiae OXA1 gene is required for the correct assembly of cytochrome c oxidase and oligomycin-sensitive ATP synthase.","date":"1996","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/8612730","citation_count":123,"is_preprint":false},{"pmid":"29281821","id":"PMC_29281821","title":"Identification of Oxa1 Homologs Operating in the Eukaryotic Endoplasmic Reticulum.","date":"2017","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/29281821","citation_count":114,"is_preprint":false},{"pmid":"8067742","id":"PMC_8067742","title":"Emergence of clinical isolates of Escherichia coli producing TEM-1 derivatives or an OXA-1 beta-lactamase conferring resistance to beta-lactamase inhibitors.","date":"1994","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/8067742","citation_count":113,"is_preprint":false},{"pmid":"19450532","id":"PMC_19450532","title":"YidC and Oxa1 form dimeric insertion pores on the translating ribosome.","date":"2009","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/19450532","citation_count":102,"is_preprint":false},{"pmid":"14507478","id":"PMC_14507478","title":"The Alb3/Oxa1/YidC protein family: membrane-localized chaperones facilitating membrane protein insertion?","date":"2003","source":"Trends in cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/14507478","citation_count":101,"is_preprint":false},{"pmid":"7991568","id":"PMC_7991568","title":"Cloning of a human gene involved in cytochrome oxidase assembly by functional complementation of an oxa1- mutation in Saccharomyces cerevisiae.","date":"1994","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/7991568","citation_count":94,"is_preprint":false},{"pmid":"25947384","id":"PMC_25947384","title":"YidC/Alb3/Oxa1 Family of Insertases.","date":"2015","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/25947384","citation_count":90,"is_preprint":false},{"pmid":"12191770","id":"PMC_12191770","title":"Insertion of proteins into the inner membrane of mitochondria: the role of the Oxa1 complex.","date":"2002","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/12191770","citation_count":88,"is_preprint":false},{"pmid":"17344477","id":"PMC_17344477","title":"Oxa1 directly interacts with Atp9 and mediates its assembly into the mitochondrial F1Fo-ATP synthase complex.","date":"2007","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/17344477","citation_count":84,"is_preprint":false},{"pmid":"20800571","id":"PMC_20800571","title":"Inserting membrane proteins: the YidC/Oxa1/Alb3 machinery in bacteria, mitochondria, and chloroplasts.","date":"2010","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/20800571","citation_count":83,"is_preprint":false},{"pmid":"17936786","id":"PMC_17936786","title":"Knockdown of human Oxa1l impairs the biogenesis of F1Fo-ATP synthase and NADH:ubiquinone oxidoreductase.","date":"2007","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/17936786","citation_count":78,"is_preprint":false},{"pmid":"11823466","id":"PMC_11823466","title":"The Oxa1 protein forms a homooligomeric complex and is an essential part of the mitochondrial export translocase in Neurospora crassa.","date":"2002","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11823466","citation_count":72,"is_preprint":false},{"pmid":"18522806","id":"PMC_18522806","title":"Roles of Oxa1-related inner-membrane translocases in assembly of respiratory chain complexes.","date":"2008","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/18522806","citation_count":70,"is_preprint":false},{"pmid":"10816574","id":"PMC_10816574","title":"Absence of the mitochondrial AAA protease Yme1p restores F0-ATPase subunit accumulation in an oxa1 deletion mutant of Saccharomyces cerevisiae.","date":"2000","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10816574","citation_count":68,"is_preprint":false},{"pmid":"12586834","id":"PMC_12586834","title":"Complementary impact of paralogous Oxa1-like proteins of Bacillus subtilis on post-translocational stages in protein secretion.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12586834","citation_count":62,"is_preprint":false},{"pmid":"30201738","id":"PMC_30201738","title":"OXA1L mutations cause mitochondrial encephalopathy and a combined oxidative phosphorylation defect.","date":"2018","source":"EMBO molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/30201738","citation_count":61,"is_preprint":false},{"pmid":"14767059","id":"PMC_14767059","title":"The Oxa2 protein of Neurospora crassa plays a critical role in the biogenesis of cytochrome oxidase and defines a ubiquitous subbranch of the Oxa1/YidC/Alb3 protein family.","date":"2004","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/14767059","citation_count":61,"is_preprint":false},{"pmid":"16092528","id":"PMC_16092528","title":"Oxa1/Alb3/YidC system for insertion of membrane proteins in mitochondria, chloroplasts and bacteria (review).","date":"2005","source":"Molecular membrane biology","url":"https://pubmed.ncbi.nlm.nih.gov/16092528","citation_count":53,"is_preprint":false},{"pmid":"16669040","id":"PMC_16669040","title":"Iron uptake by plants from microbial siderophores : a study with 7-nitrobenz-2 oxa-1,3-diazole-desferrioxamine as fluorescent ferrioxamine B analog.","date":"1992","source":"Plant physiology","url":"https://pubmed.ncbi.nlm.nih.gov/16669040","citation_count":51,"is_preprint":false},{"pmid":"33664512","id":"PMC_33664512","title":"Structural and molecular mechanisms for membrane protein biogenesis by the Oxa1 superfamily.","date":"2021","source":"Nature structural & molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/33664512","citation_count":49,"is_preprint":false},{"pmid":"24647004","id":"PMC_24647004","title":"Detection of OXA-1 β-lactamase gene of Klebsiella pneumoniae from blood stream infections (BSI) by conventional PCR and in-silico analysis to understand the mechanism of OXA mediated resistance.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24647004","citation_count":48,"is_preprint":false},{"pmid":"21194367","id":"PMC_21194367","title":"Evolution of YidC/Oxa1/Alb3 insertases: three independent gene duplications followed by functional specialization in bacteria, mitochondria and chloroplasts.","date":"2011","source":"Biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21194367","citation_count":47,"is_preprint":false},{"pmid":"16905652","id":"PMC_16905652","title":"The synechocystis sp PCC 6803 oxa1 homolog is essential for membrane integration of reaction center precursor protein pD1.","date":"2006","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/16905652","citation_count":46,"is_preprint":false},{"pmid":"19485421","id":"PMC_19485421","title":"Mutation of the active site carboxy-lysine (K70) of OXA-1 beta-lactamase results in a deacylation-deficient enzyme.","date":"2009","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19485421","citation_count":43,"is_preprint":false},{"pmid":"19783770","id":"PMC_19783770","title":"Mapping of the Saccharomyces cerevisiae Oxa1-mitochondrial ribosome interface and identification of MrpL40, a ribosomal protein in close proximity to Oxa1 and critical for oxidative phosphorylation complex assembly.","date":"2009","source":"Eukaryotic cell","url":"https://pubmed.ncbi.nlm.nih.gov/19783770","citation_count":41,"is_preprint":false},{"pmid":"20601428","id":"PMC_20601428","title":"Properties of the C-terminal tail of human mitochondrial inner membrane protein Oxa1L and its interactions with mammalian mitochondrial ribosomes.","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20601428","citation_count":40,"is_preprint":false},{"pmid":"22829595","id":"PMC_22829595","title":"The mitochondrial oxidase assembly protein1 (Oxa1) insertase forms a membrane pore in lipid bilayers.","date":"2012","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22829595","citation_count":39,"is_preprint":false},{"pmid":"15355998","id":"PMC_15355998","title":"A yeast mitochondrial membrane methyltransferase-like protein can compensate for oxa1 mutations.","date":"2004","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15355998","citation_count":35,"is_preprint":false},{"pmid":"21742679","id":"PMC_21742679","title":"False extended-spectrum {beta}-lactamase phenotype in clinical isolates of Escherichia coli associated with increased expression of OXA-1 or TEM-1 penicillinases and loss of porins.","date":"2011","source":"The Journal of antimicrobial chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/21742679","citation_count":35,"is_preprint":false},{"pmid":"19307606","id":"PMC_19307606","title":"Translocation and assembly of mitochondrially coded Saccharomyces cerevisiae cytochrome c oxidase subunit Cox2 by Oxa1 and Yme1 in the absence of Cox18.","date":"2009","source":"Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/19307606","citation_count":33,"is_preprint":false},{"pmid":"14593095","id":"PMC_14593095","title":"Protein export across the inner membrane of mitochondria: the nature of translocated domains determines the dependence on the Oxa1 translocase.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/14593095","citation_count":33,"is_preprint":false},{"pmid":"10712694","id":"PMC_10712694","title":"The respiratory gene OXA1 has two fission yeast orthologues which together encode a function essential for cellular viability.","date":"2000","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/10712694","citation_count":31,"is_preprint":false},{"pmid":"22846909","id":"PMC_22846909","title":"The membrane insertase Oxa1 is required for efficient import of carrier proteins into mitochondria.","date":"2012","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/22846909","citation_count":30,"is_preprint":false},{"pmid":"20739282","id":"PMC_20739282","title":"Identification of protein-protein and protein-ribosome interacting regions of the C-terminal tail of human mitochondrial inner membrane protein Oxa1L.","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20739282","citation_count":30,"is_preprint":false},{"pmid":"22904327","id":"PMC_22904327","title":"Oxa1-ribosome complexes coordinate the assembly of cytochrome C oxidase in mitochondria.","date":"2012","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22904327","citation_count":30,"is_preprint":false},{"pmid":"23111630","id":"PMC_23111630","title":"The YidC/Oxa1/Alb3 protein family: common principles and distinct features.","date":"2012","source":"Biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/23111630","citation_count":29,"is_preprint":false},{"pmid":"22513091","id":"PMC_22513091","title":"The inner-mitochondrial distribution of Oxa1 depends on the growth conditions and on the availability of substrates.","date":"2012","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/22513091","citation_count":29,"is_preprint":false},{"pmid":"15545650","id":"PMC_15545650","title":"Interaction between the oxa1 and rmp1 genes modulates respiratory complex assembly and life span in Podospora anserina.","date":"2004","source":"Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/15545650","citation_count":25,"is_preprint":false},{"pmid":"18559643","id":"PMC_18559643","title":"Inhibition of OXA-1 beta-lactamase by penems.","date":"2008","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/18559643","citation_count":25,"is_preprint":false},{"pmid":"35231030","id":"PMC_35231030","title":"The ER membrane complex (EMC) can functionally replace the Oxa1 insertase in mitochondria.","date":"2022","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/35231030","citation_count":24,"is_preprint":false},{"pmid":"24443569","id":"PMC_24443569","title":"The different inhibition mechanisms of OXA-1 and OXA-24 β-lactamases are determined by the stability of active site carboxylated lysine.","date":"2014","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/24443569","citation_count":24,"is_preprint":false},{"pmid":"9450344","id":"PMC_9450344","title":"Functional complementation of an oxa1- yeast mutation identifies an Arabidopsis thaliana cDNA involved in the assembly of respiratory complexes.","date":"1997","source":"The Plant journal : for cell and molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/9450344","citation_count":23,"is_preprint":false},{"pmid":"21123154","id":"PMC_21123154","title":"Detection of unrelated Escherichia coli strains harboring genes of CTX-M-15, OXA-1, and AAC(6')-Ib-cr enzymes in a Tunisian hospital and characterization of their integrons and virulence factors.","date":"2010","source":"Journal of chemotherapy (Florence, Italy)","url":"https://pubmed.ncbi.nlm.nih.gov/21123154","citation_count":22,"is_preprint":false},{"pmid":"35590320","id":"PMC_35590320","title":"Detection of carbapenemases blaOXA48-blaKPC-blaNDM-blaVIM and extended-spectrum-β-lactamase blaOXA1-blaSHV-blaTEM genes in Gram-negative bacterial isolates from ICU burns patients.","date":"2022","source":"Annals of clinical microbiology and antimicrobials","url":"https://pubmed.ncbi.nlm.nih.gov/35590320","citation_count":21,"is_preprint":false},{"pmid":"15225614","id":"PMC_15225614","title":"The Arabidopsis thaliana chloroplast inner envelope protein ARTEMIS is a functional member of the Alb3/Oxa1/YidC family of proteins.","date":"2004","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/15225614","citation_count":21,"is_preprint":false},{"pmid":"16253275","id":"PMC_16253275","title":"Conserved mechanism of Oxa1 insertion into the mitochondrial inner membrane.","date":"2005","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/16253275","citation_count":20,"is_preprint":false},{"pmid":"3019237","id":"PMC_3019237","title":"Analysis by using DNA probes of the OXA-1 beta-lactamase gene and its transposon.","date":"1986","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/3019237","citation_count":20,"is_preprint":false},{"pmid":"38199007","id":"PMC_38199007","title":"Identification of TMEM126A as OXA1L-interacting protein reveals cotranslational quality control in mitochondria.","date":"2024","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/38199007","citation_count":18,"is_preprint":false},{"pmid":"26295796","id":"PMC_26295796","title":"Reduced Susceptibility to Cefepime in Clinical Isolates of Enterobacteriaceae Producing OXA-1 Beta-Lactamase.","date":"2015","source":"Microbial drug resistance (Larchmont, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/26295796","citation_count":18,"is_preprint":false},{"pmid":"19349278","id":"PMC_19349278","title":"Topogenesis of mammalian Oxa1, a component of the mitochondrial inner membrane protein export machinery.","date":"2009","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19349278","citation_count":16,"is_preprint":false},{"pmid":"22429123","id":"PMC_22429123","title":"Site-saturation mutagenesis of position V117 in OXA-1 β-lactamase: effect of side chain polarity on enzyme carboxylation and substrate turnover.","date":"2012","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22429123","citation_count":16,"is_preprint":false},{"pmid":"29310909","id":"PMC_29310909","title":"Oxa1 Superfamily: New Members Found in the ER.","date":"2018","source":"Trends in biochemical sciences","url":"https://pubmed.ncbi.nlm.nih.gov/29310909","citation_count":14,"is_preprint":false},{"pmid":"30103014","id":"PMC_30103014","title":"Draft genome sequence of an NDM-5, CTX-M-15 and OXA-1 co-producing Escherichia coli ST167 clinical strain isolated from a urine sample.","date":"2018","source":"Journal of global antimicrobial resistance","url":"https://pubmed.ncbi.nlm.nih.gov/30103014","citation_count":13,"is_preprint":false},{"pmid":"3010839","id":"PMC_3010839","title":"Genesis of a complex transposon encoding the OXA-1 (type II) beta-lactamase gene.","date":"1985","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/3010839","citation_count":13,"is_preprint":false},{"pmid":"16435202","id":"PMC_16435202","title":"Mutation detection in four candidate genes (OXA1L, MRS2L, YME1L and MIPEP) for combined deficiencies in the oxidative phosphorylation system.","date":"2005","source":"Journal of inherited metabolic disease","url":"https://pubmed.ncbi.nlm.nih.gov/16435202","citation_count":11,"is_preprint":false},{"pmid":"30032071","id":"PMC_30032071","title":"Polymorphisms in the DAD1 and OXA1L genes are associated with asthma and atopy in a South American population.","date":"2018","source":"Molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/30032071","citation_count":10,"is_preprint":false},{"pmid":"21767713","id":"PMC_21767713","title":"Characterization of a novel extended-spectrum β-lactamase phenotype from OXA-1 expression in Salmonella Typhimurium strains from Africa and Ireland.","date":"2011","source":"Diagnostic microbiology and infectious disease","url":"https://pubmed.ncbi.nlm.nih.gov/21767713","citation_count":9,"is_preprint":false},{"pmid":"9247084","id":"PMC_9247084","title":"Sequence and structure of the human OXA1L gene and its upstream elements.","date":"1997","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/9247084","citation_count":8,"is_preprint":false},{"pmid":"34965471","id":"PMC_34965471","title":"Genomic characterisation of Escherichia coli isolates co-producing NDM-5 and OXA-1 from hospitalised patients with invasive infections.","date":"2021","source":"Journal of global antimicrobial resistance","url":"https://pubmed.ncbi.nlm.nih.gov/34965471","citation_count":7,"is_preprint":false},{"pmid":"32579605","id":"PMC_32579605","title":"ZapE/Afg1 interacts with Oxa1 and its depletion causes a multifaceted phenotype.","date":"2020","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/32579605","citation_count":7,"is_preprint":false},{"pmid":"33363717","id":"PMC_33363717","title":"β-lactamases (bla  ) and class C β-lactamases gene frequency in Pseudomonas aeruginosa isolated from various clinical specimens in Khartoum State, Sudan: a cross sectional study.","date":"2020","source":"F1000Research","url":"https://pubmed.ncbi.nlm.nih.gov/33363717","citation_count":7,"is_preprint":false},{"pmid":"19854151","id":"PMC_19854151","title":"Mammalian Oxa1 protein is useful for assessment of submitochondrial protein localization and mitochondrial membrane integrity.","date":"2009","source":"Analytical biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19854151","citation_count":7,"is_preprint":false},{"pmid":"15908145","id":"PMC_15908145","title":"The transcriptional activator HAP4 is a high copy suppressor of an oxa1 yeast mutation.","date":"2005","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/15908145","citation_count":7,"is_preprint":false},{"pmid":"11717515","id":"PMC_11717515","title":"Crystallization and preliminary X-ray study of OXA-1, a class D beta-lactamase.","date":"2001","source":"Acta crystallographica. Section D, Biological crystallography","url":"https://pubmed.ncbi.nlm.nih.gov/11717515","citation_count":7,"is_preprint":false},{"pmid":"36416539","id":"PMC_36416539","title":"Evaluation of Piperacillin-Tazobactam ETEST for the Detection of OXA-1 Resistance Mechanism among Escherichia coli and Klebsiella pneumoniae.","date":"2022","source":"Journal of clinical microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/36416539","citation_count":6,"is_preprint":false},{"pmid":"25102723","id":"PMC_25102723","title":"Clonal spread of Klebsiella pneumoniae producing OXA-1 betalactamase in a Spanish hospital.","date":"2013","source":"International microbiology : the official journal of the Spanish Society for Microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/25102723","citation_count":6,"is_preprint":false},{"pmid":"6397946","id":"PMC_6397946","title":"Different mechanisms of TEM-1 and Oxa-1 mediated resistance to piperacillin in E. coli.","date":"1984","source":"Zentralblatt fur Bakteriologie, Mikrobiologie, und Hygiene. Series A, Medical microbiology, infectious diseases, virology, parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/6397946","citation_count":5,"is_preprint":false},{"pmid":"20025673","id":"PMC_20025673","title":"A mutational analysis reveals new functional interactions between domains of the Oxa1 protein in Saccharomyces cerevisiae.","date":"2009","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/20025673","citation_count":5,"is_preprint":false},{"pmid":"24472117","id":"PMC_24472117","title":"The SFT-1 and OXA-1 respiratory chain complex assembly factors influence lifespan by distinct mechanisms in C. elegans.","date":"2013","source":"Longevity & healthspan","url":"https://pubmed.ncbi.nlm.nih.gov/24472117","citation_count":5,"is_preprint":false},{"pmid":"40551575","id":"PMC_40551575","title":"OXA1L deficiency causes mitochondrial myopathy via reactive oxygen species regulated nuclear factor kappa B signalling pathway.","date":"2025","source":"Clinical and translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/40551575","citation_count":3,"is_preprint":false},{"pmid":"34458404","id":"PMC_34458404","title":"Purification of Mitochondrial Ribosomes with the Translocase Oxa1L from HEK Cells.","date":"2021","source":"Bio-protocol","url":"https://pubmed.ncbi.nlm.nih.gov/34458404","citation_count":3,"is_preprint":false},{"pmid":"23198851","id":"PMC_23198851","title":"Partial suppression of Oxa1 mutants by mitochondria-targeted signal recognition particle provides insights into the evolution of the cotranslational insertion systems.","date":"2013","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/23198851","citation_count":3,"is_preprint":false},{"pmid":"39347609","id":"PMC_39347609","title":"Palladium-Catalyzed [7 + 5] and Higher-Order Annulations of Oxa-1,n-dipoles: Synthesis of 12- to 15-Membered Lactones.","date":"2024","source":"Organic letters","url":"https://pubmed.ncbi.nlm.nih.gov/39347609","citation_count":2,"is_preprint":false},{"pmid":"39615807","id":"PMC_39615807","title":"New variants of the DAD1 and OXA1L genes are associated with asthma and atopy in an adult population.","date":"2024","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/39615807","citation_count":1,"is_preprint":false},{"pmid":"10410243","id":"PMC_10410243","title":"Expression of the divergent transcription unit containing the yeast PET122 and OXA1 genes.","date":"1999","source":"Biochemistry and molecular biology international","url":"https://pubmed.ncbi.nlm.nih.gov/10410243","citation_count":1,"is_preprint":false},{"pmid":"40497048","id":"PMC_40497048","title":"Identification of an IncHI5-like plasmid co-harboring bla NDM-1 and bla OXA-1 in mcr-8.1-positive Klebsiella pneumoniae isolate.","date":"2025","source":"Frontiers in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/40497048","citation_count":1,"is_preprint":false},{"pmid":"37108900","id":"PMC_37108900","title":"A Correlation between 3'-UTR of OXA1 Gene and Yeast Mitochondrial Translation.","date":"2023","source":"Journal of fungi (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/37108900","citation_count":0,"is_preprint":false},{"pmid":"37834108","id":"PMC_37834108","title":"NMR-Based Characterization of the Interaction between Yeast Oxa1-CTD and Ribosomes.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37834108","citation_count":0,"is_preprint":false},{"pmid":"41602100","id":"PMC_41602100","title":"Correlation of OXA-1 and TEM-1 genes with antibiotic resistance to piperacillin/tazobactam in ESBL-producing Enterobacterales: insights from a multi-center analysis.","date":"2026","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/41602100","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.06.05.658076","title":"Functional redundancy in Oxa1-family insertases supports robust membrane insertion of influenza A virus M2 viroporin","date":"2025-06-06","source":"bioRxiv","url":"https://doi.org/10.1101/2025.06.05.658076","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.07.01.662679","title":"Spatio-temporal mass spectrometry in living cells reveals regulators of cuproptosis","date":"2025-07-03","source":"bioRxiv","url":"https://doi.org/10.1101/2025.07.01.662679","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.06.27.600981","title":"A priority code in presequences: mitochondrial targeting signals assign specific import characteristics to precursor proteins","date":"2024-06-27","source":"bioRxiv","url":"https://doi.org/10.1101/2024.06.27.600981","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.12.13.628402","title":"YibN, a bona fide interactor of YidC with implications in membrane protein insertion and membrane lipid production","date":"2024-12-14","source":"bioRxiv","url":"https://doi.org/10.1101/2024.12.13.628402","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.05.26.656142","title":"Substrate-induced assembly and functional mechanism of the bacterial membrane protein insertase SecYEG-YidC","date":"2025-05-27","source":"bioRxiv","url":"https://doi.org/10.1101/2025.05.26.656142","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":40777,"output_tokens":4597,"usd":0.095643},"stage2":{"model":"claude-opus-4-6","input_tokens":8140,"output_tokens":2698,"usd":0.162225},"total_usd":0.257868,"stage1_batch_id":"msgbatch_012ZiiCUBfB62NCTQd4Bk1Jo","stage2_batch_id":"msgbatch_01Xuqq9aUHoQouS7UVGZNStZ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1994,\n      \"finding\": \"The yeast OXA1 nuclear gene product is required post-translationally for cytochrome c oxidase biogenesis and assembly; null mutations abolish cytochrome aa3 and reduce cytochrome b, with mitochondrially encoded COX subunits still synthesized but assembly impaired.\",\n      \"method\": \"Genetic analysis, cytochrome spectra, gene disruption (oxa1::LEU2)\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with defined biochemical phenotype, replicated by complementation and disruption alleles\",\n      \"pmids\": [\"8196054\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1994,\n      \"finding\": \"A human OXA1L cDNA functionally complements yeast oxa1 mutants and restores cytochrome oxidase assembly, demonstrating conserved function between yeast Oxa1 and human OXA1L.\",\n      \"method\": \"Genetic complementation, oxygen consumption measurements, cytochrome absorption spectra\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — functional rescue across species with multiple biochemical readouts\",\n      \"pmids\": [\"7991568\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1996,\n      \"finding\": \"Yeast Oxa1p is required for correct assembly of both cytochrome c oxidase and oligomycin-sensitive ATP synthase, as shown by absence of heme aa3, loss of cytochrome c oxidoreductase activity, and dramatic decrease of oligomycin-sensitive ATPase in deletion strains.\",\n      \"method\": \"Cytochrome spectra, enzymatic activity measurements, non-denaturing PAGE analysis of respiratory complexes\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — KO with multiple orthogonal biochemical readouts\",\n      \"pmids\": [\"8612730\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Oxa1 forms a homooligomeric complex of ~170-180 kDa (likely a tetramer) in the Neurospora crassa mitochondrial inner membrane and is an essential component of the OXA translocase.\",\n      \"method\": \"Native complex isolation, biochemical fractionation, molecular weight analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — single lab, direct biochemical isolation of complex\",\n      \"pmids\": [\"11823466\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"The matrix-exposed C-terminus of yeast Oxa1 forms an alpha-helical domain that binds to mitochondrial ribosomes (large subunit), and deletion of this domain strongly reduces co-translational membrane insertion efficiency of mitochondrially encoded Cox2.\",\n      \"method\": \"Ribosome binding assays, deletion analysis, import and insertion assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal binding assays plus functional deletion phenotype, independently replicated (PMID 14657017 and 14657018)\",\n      \"pmids\": [\"14657018\", \"14657017\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Yeast Oxa1 physically associates with the large mitochondrial ribosomal subunit; the C-terminal region mediates this interaction, and Oxa1 can be crosslinked to Mrp20 (homolog of bacterial L23, located near the peptide exit tunnel).\",\n      \"method\": \"Co-sedimentation, chemical crosslinking, reciprocal Co-IP\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (crosslinking + co-sedimentation), replicated in two simultaneous publications\",\n      \"pmids\": [\"14657017\", \"14657018\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"The dependence of protein domains on the Oxa1 translocase for export across the mitochondrial inner membrane correlates with the net charge of the translocated domain, not its position in the sequence.\",\n      \"method\": \"Genetic and biochemical analysis using fusion proteins in yeast mitochondria\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis combined with biochemical insertion assays\",\n      \"pmids\": [\"14593095\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Yeast Oxa1 directly and physically interacts with newly synthesized mitochondrially encoded Atp9 (F1Fo-ATP synthase subunit c) in a posttranslational manner, and is required for the assembly of the Atp9-F1 subcomplex with subunit Atp6; this interaction does not require the C-terminal matrix region of Oxa1.\",\n      \"method\": \"Co-immunoprecipitation, pulse-chase analysis, blue native PAGE\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct Co-IP with pulse-chase plus assembly analysis by BN-PAGE\",\n      \"pmids\": [\"17344477\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Human OXA1L (42 kDa) localizes exclusively to mitochondria as an integral inner membrane protein and is part of a 600-700 kDa complex; shRNA-mediated knockdown reduces F1Fo-ATP synthase steady-state levels and activity and moderately reduces complex I, but does not affect cytochrome c oxidase (complex IV) or cytochrome bc1 (complex III).\",\n      \"method\": \"shRNA knockdown, 2D BN/denaturing PAGE, ATPase activity assay, fractionation, FLAG-tagging and immunolocalization\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — stable KD with multiple orthogonal biochemical readouts\",\n      \"pmids\": [\"17936786\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Cryo-EM structures of yeast Oxa1 bound to E. coli ribosome nascent-chain complexes show that Oxa1 forms dimers positioned above the ribosomal tunnel exit; conserved transmembrane helices localize to the dimer interface; Oxa1 contacts ribosomal protein L23 and conserved rRNA helices H59 and H24.\",\n      \"method\": \"Cryo-electron microscopy, cysteine crosslinking\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — cryo-EM structure with crosslinking validation\",\n      \"pmids\": [\"19450532\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"The C-terminal tail of human Oxa1L (Oxa1L-CTT) binds to mammalian mitochondrial ribosomes with a Kd of 0.3-0.8 µM and a stoichiometry of 2; it crosslinks to mammalian mitochondrial homologs of ribosomal proteins L13, L20, L28, and mitochondria-specific proteins MRPL48, MRPL49, and MRPL51 — a binding interface distinct from the conventional peptide exit tunnel.\",\n      \"method\": \"Fluorescence binding assays, chemical crosslinking, mass spectrometry\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — quantitative binding analysis plus crosslinking with protein identification\",\n      \"pmids\": [\"20601428\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Mammalian Oxa1 has five transmembrane segments and adopts an N-out (IMS), C-in (matrix) topology; a conserved hexapeptide (GLPWWG) near TM1 is essential for correct topogenesis including export of the N-terminal segment to the IMS; all five TMs cooperatively mediate membrane integration.\",\n      \"method\": \"Systematic deletion/mutation constructs in HeLa cells, protease protection assays, alkaline extraction\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — systematic mutagenesis with functional topology mapping\",\n      \"pmids\": [\"19349278\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"During its own biogenesis, Oxa1 initially accumulates at Tim23 (the inner membrane protein translocase) and requires mtHsp70 for presequence cleavage, but membrane insertion of the mature protein is mtHsp70-independent, indicating Oxa1 accepts preproteins within the membrane from Tim23.\",\n      \"method\": \"Import assays in yeast mitochondria, co-immunoprecipitation with Tim23, use of mtHsp70 mutants\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — import assays with defined mutants and co-IP, single lab\",\n      \"pmids\": [\"16253275\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"The C-terminal tail of human Oxa1L (Oxa1L-CTT) does not form a stable coiled-coil in solution (contrary to yeast), but forms oligomers cooperatively in a submicromolar range; contacts near a long helix around position 39 mediate oligomer formation; the tail undergoes conformational changes and induced oligomerization upon ribosome binding.\",\n      \"method\": \"Fluorescence anisotropy, fluorescence lifetime measurements, fluorescence correlation spectroscopy\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — biophysical characterization with multiple fluorescence methods, single lab\",\n      \"pmids\": [\"20739282\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Purified and reconstituted yeast Oxa1 forms a cation-selective protein-conducting channel that specifically responds to mitochondrial export signals; single-channel analysis revealed four discrete channels per active unit, suggesting a tetrameric pore with a restriction zone diameter of 0.6-2 nm sufficient for polypeptide translocation.\",\n      \"method\": \"Protein purification, reconstitution into lipid bilayers, electrophysiology/single-channel analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — in vitro reconstitution with electrophysiology and functional characterization\",\n      \"pmids\": [\"22829595\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Insertion of flexible linkers between the Oxa1 insertase domain and ribosome-binding region causes length-dependent defects in cytochrome c oxidase assembly (not just membrane insertion), demonstrating that close proximity of Oxa1 to ribosomes is critical for productive assembly coordination of COX subunits.\",\n      \"method\": \"Yeast genetics, linker insertion mutagenesis, respiratory activity measurements, immunoblotting\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — systematic mutagenesis with functional readout, single lab\",\n      \"pmids\": [\"22904327\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Oxa1 is required for efficient import and biogenesis of mitochondrial carrier proteins (including Aac2/ATP-ADP carrier), which are inserted from the IMS side and lack bacterial homologs, expanding the known substrate spectrum of Oxa1 beyond conserved endosymbiotic proteins.\",\n      \"method\": \"Temperature-sensitive oxa1 mutant, in vitro import assays, steady-state level analysis\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — novel temperature-sensitive mutant with in vitro import assays, single lab\",\n      \"pmids\": [\"22846909\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Yeast Oxa1 distribution between the inner boundary membrane (IBM) and cristae membrane (CM) is dynamic: enriched in IBM under fermentable conditions (driven by nuclear-encoded substrate import) and in CM under respiratory conditions (requiring both mitochondrial translation and the ribosome-binding domain of Oxa1).\",\n      \"method\": \"STED superresolution microscopy, fractionation, genetic deletion of ribosome-binding domain\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct superresolution imaging combined with genetic manipulations\",\n      \"pmids\": [\"22513091\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Human OXA1L is required for the assembly of multiple respiratory chain complexes (I, IV, and V); immunoprecipitation of OXA1L enriches mtDNA-encoded subunits of complexes I, IV, and V; expression of wild-type OXA1L in patient fibroblasts with biallelic OXA1L variants rescues complex IV and V defects.\",\n      \"method\": \"Whole exome sequencing, patient cell complementation, targeted OXA1L depletion in human cells and Drosophila, immunoprecipitation-mass spectrometry, BN-PAGE\",\n      \"journal\": \"EMBO molecular medicine\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — patient variant functional validation by complementation, Co-IP/MS, and multiple model systems\",\n      \"pmids\": [\"30201738\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"NMR analysis of yeast Oxa1-CTD reveals it forms a transient α-helical structure within residues P342-Q385; two conserved ribosome contact sites were identified: a N-terminal site (V321-I327) and a central stretch (I348-Q370) that transitions from transient to stable helix upon ribosome binding.\",\n      \"method\": \"NMR spectroscopy, chemical shift perturbation analysis with E. coli 70S ribosomes\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 — NMR structural characterization with ribosome interaction mapping, single lab\",\n      \"pmids\": [\"37834108\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TMEM126A is a physical interactor of human OXA1L; TMEM126A associates with mitochondrial ribosomes and translation products and cooperates with OXA1L in cotranslational protein insertion into the inner membrane; loss of TMEM126A destabilizes mitochondrial translation products, which together with cargo-blocked OXA1L are degraded by the mitochondrial iAAA protease.\",\n      \"method\": \"Co-immunoprecipitation, proximity labeling, ribosome association assays, iAAA protease degradation assays\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP plus functional characterization with protease degradation pathway, multiple orthogonal methods\",\n      \"pmids\": [\"38199007\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"OXA1L deficiency in skeletal muscle cells causes combined mitochondrial respiratory chain defects and OXPHOS impairments; elevated ROS production resulting from OXPHOS dysfunction activates the NF-κB signalling pathway, triggering apoptosis; wild-type but not truncated mutant OXA1L rescues respiratory chain defects in KO cells.\",\n      \"method\": \"hiPSC differentiation, CRISPR/Cas9 KO, conditional skeletal muscle KO mouse model, complementation with WT vs mutant OXA1L\",\n      \"journal\": \"Clinical and translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple model systems with complementation controls, single lab\",\n      \"pmids\": [\"40551575\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"OXA1L (human) / Oxa1 (yeast) is a conserved integral inner mitochondrial membrane insertase that co-translationally inserts mtDNA-encoded subunits of respiratory chain complexes I, IV, and V into the inner membrane by forming a homo-oligomeric, cation-selective protein-conducting channel; its matrix-exposed C-terminal tail directly binds the large mitochondrial ribosomal subunit (via specific ribosomal proteins distinct from the canonical exit-tunnel contacts) to couple translation with membrane insertion, and it additionally cooperates with the newly identified partner TMEM126A for cotranslational quality control, with cargo-blocked OXA1L complexes cleared by the iAAA protease.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"OXA1L is a conserved integral inner mitochondrial membrane insertase that co-translationally inserts mtDNA-encoded subunits of oxidative phosphorylation complexes I, IV, and V into the inner membrane [PMID:8196054, PMID:7991568, PMID:30201738]. It forms a homo-oligomeric, cation-selective protein-conducting channel with four discrete pores sufficient for polypeptide translocation, and its matrix-exposed C-terminal tail directly binds the large mitochondrial ribosomal subunit—contacting ribosomal proteins distinct from the canonical peptide exit tunnel in mammals—to couple translation with membrane insertion [PMID:22829595, PMID:20601428, PMID:14657018]. OXA1L cooperates with TMEM126A for cotranslational quality control, and cargo-blocked OXA1L complexes are cleared by the mitochondrial iAAA protease [PMID:38199007]. Biallelic loss-of-function variants in OXA1L cause combined OXPHOS deficiency with severe encephalopathy, and OXA1L deficiency in skeletal muscle triggers ROS-mediated NF-κB activation and apoptosis [PMID:30201738, PMID:40551575].\",\n  \"teleology\": [\n    {\n      \"year\": 1994,\n      \"claim\": \"Establishing OXA1L as a conserved mitochondrial assembly factor: yeast Oxa1 was shown to be required for cytochrome c oxidase biogenesis, and human OXA1L cDNA functionally rescued the yeast null mutant, demonstrating deep functional conservation of a membrane protein insertase.\",\n      \"evidence\": \"Gene disruption in yeast with cytochrome spectra and respiratory measurements; cross-species complementation of yeast oxa1Δ by human OXA1L\",\n      \"pmids\": [\"8196054\", \"7991568\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Substrate range beyond complex IV not yet defined\", \"Mechanism of insertion (channel vs chaperone) unknown\", \"Topology of Oxa1 in the membrane not determined\"]\n    },\n    {\n      \"year\": 1996,\n      \"claim\": \"The substrate repertoire was expanded beyond complex IV: Oxa1 was also required for oligomycin-sensitive ATP synthase assembly, establishing it as a general insertase for multiple OXPHOS complexes.\",\n      \"evidence\": \"Enzymatic activity measurements and BN-PAGE of respiratory complexes in yeast oxa1Δ\",\n      \"pmids\": [\"8612730\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether complex I (absent in yeast) is also a substrate remained unknown\", \"Whether Oxa1 acts co- or post-translationally not resolved\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"The mechanism coupling translation to insertion was revealed: the C-terminal matrix tail of Oxa1 binds the large mitochondrial ribosomal subunit near the peptide exit tunnel, and this interaction is required for efficient co-translational membrane insertion.\",\n      \"evidence\": \"Ribosome co-sedimentation, chemical crosslinking to Mrp20/L23, deletion analysis with Cox2 insertion assays in yeast\",\n      \"pmids\": [\"14657018\", \"14657017\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Binding interface on mammalian mitoribosome not yet mapped\", \"Structural basis of the Oxa1-ribosome interaction unknown\", \"Whether oligomerization is functionally linked to ribosome binding unclear\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"OXA1L function was characterized in mammalian cells: human OXA1L resides in a ~600-700 kDa inner membrane complex, and its depletion primarily reduces ATP synthase and complex I levels, revealing a partially distinct substrate hierarchy compared to yeast.\",\n      \"evidence\": \"shRNA knockdown in human cells with 2D BN/SDS-PAGE, ATPase activity assays, and FLAG-tag immunolocalization\",\n      \"pmids\": [\"17936786\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Why complex IV was unaffected in human KD (unlike yeast) not explained\", \"Identity of co-complex partners in the 600-700 kDa assembly unknown\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Structural and biophysical work defined the insertase architecture and its ribosome-binding mode: cryo-EM showed Oxa1 dimers docked above the ribosomal exit tunnel; the human OXA1L C-terminal tail binds mitoribosomes at a site involving L13, L20, L28, MRPL48, MRPL49, and MRPL51—distinct from the canonical exit tunnel contacts; and mammalian Oxa1L was shown to have five transmembrane segments with N-out/C-in topology.\",\n      \"evidence\": \"Cryo-EM of Oxa1-ribosome complexes, fluorescence binding assays with Kd measurement, crosslinking-MS, systematic deletion/topology mapping in HeLa cells\",\n      \"pmids\": [\"19450532\", \"20601428\", \"19349278\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"High-resolution structure of the transmembrane channel not available\", \"Whether the mammalian binding interface functions identically to the yeast one not tested in vivo\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"The protein-conducting channel was reconstituted and characterized: Oxa1 forms a cation-selective channel with four discrete conductance states responsive to mitochondrial export signals, consistent with a tetrameric pore; close proximity of the insertase to ribosomes was shown to be critical not just for insertion but for downstream assembly of COX subunits.\",\n      \"evidence\": \"Reconstitution into lipid bilayers with single-channel electrophysiology; linker-insertion mutagenesis with respiratory function assays in yeast\",\n      \"pmids\": [\"22829595\", \"22904327\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Pore structure at atomic resolution not determined\", \"How the channel discriminates substrates from non-substrates mechanistically unclear\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Clinical relevance and full human substrate spectrum were established: biallelic OXA1L variants cause combined OXPHOS deficiency with severe encephalopathy; OXA1L physically associates with mtDNA-encoded subunits of complexes I, IV, and V, and wild-type OXA1L rescues patient cell defects.\",\n      \"evidence\": \"Whole-exome sequencing of patients, complementation in patient fibroblasts, IP-MS, and Drosophila OXA1L depletion\",\n      \"pmids\": [\"30201738\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Genotype-phenotype correlations across different OXA1L mutations not established\", \"Whether partial loss of function produces tissue-specific phenotypes not explored\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"A cotranslational quality-control pathway was uncovered: TMEM126A was identified as a physical partner of OXA1L that cooperates in cotranslational insertion; when TMEM126A is lost, translation products are destabilized and cargo-blocked OXA1L complexes are degraded by the iAAA protease.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation, proximity labeling, ribosome association assays, iAAA protease degradation assays in human cells\",\n      \"pmids\": [\"38199007\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of OXA1L-TMEM126A interaction not resolved\", \"Whether iAAA-mediated clearance is a general surveillance mechanism for all insertase substrates unknown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Downstream pathological consequences of OXA1L loss were delineated in muscle: OXA1L deficiency causes OXPHOS impairment leading to elevated ROS, NF-κB activation, and apoptosis in skeletal muscle.\",\n      \"evidence\": \"hiPSC-derived skeletal muscle cells, CRISPR KO, conditional muscle KO mouse, complementation with WT vs truncated mutant\",\n      \"pmids\": [\"40551575\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether NF-κB activation is a direct ROS effect or involves intermediate signaling not resolved\", \"Tissue-specific vulnerability across different OXA1L mutations not systematically compared\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A high-resolution structure of the OXA1L transmembrane channel in complex with a nascent chain and the human mitoribosome is still lacking, which would clarify substrate recognition, the mechanism of lateral release into the lipid bilayer, and functional coordination with TMEM126A.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No atomic-resolution structure of the human OXA1L channel\", \"Mechanism of lateral gate opening for substrate release into lipid bilayer unknown\", \"How OXA1L distinguishes co- from post-translational substrates mechanistically unresolved\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005215\", \"supporting_discovery_ids\": [14, 6, 11]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 2, 8, 18]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [8, 11, 17]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": []},\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [0, 2, 8, 18]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [4, 5, 10, 20]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [8, 17, 18]}\n    ],\n    \"complexes\": [\n      \"OXA1L homo-oligomeric insertase complex\",\n      \"OXA1L-TMEM126A cotranslational insertion complex\"\n    ],\n    \"partners\": [\n      \"TMEM126A\",\n      \"MRPL13\",\n      \"MRPL20\",\n      \"MRPL28\",\n      \"MRPL48\",\n      \"MRPL49\",\n      \"MRPL51\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}