OLA1 (Obg-like ATPase 1) is a universally conserved P-loop NTPase belonging to the YchF subfamily of the Obg family. Despite evolutionary relationship to GTPases, OLA1 is biochemically an ATPase that preferentially hydrolyzes ATP over GTP due to a mutation in its G4 motif. OLA1 acts as a critical regulator of translation through ribosome binding and interaction with eIF2, modulates cellular stress responses including heat shock and oxidative stress, and interacts with BRCA1/BARD1 at centrosomes for genome stability maintenance.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred cytoplasmic localization is strongly supported by experimental evidence showing OLA1 is predominantly a cytosolic protein that performs its ribosome binding and translation regulatory functions in the cytoplasm. Reason: IBA annotation is well-supported by multiple lines of experimental evidence. OLA1 functions primarily in the cytoplasm where it interacts with ribosomes, eIF2, and performs its core ATPase and translation regulatory activities. Supporting Evidence: PMID:17430889 human homologue of YchF and found that it binds and hydrolyzes ATP more efficiently than GTP GO_REF:0000054 Gene Ontology annotation based on curation of intracellular localizations of expressed fusion proteins in living cells |
| GO:0016887 ATP hydrolysis activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred ATP hydrolysis activity is directly confirmed by crystal structure and biochemical studies demonstrating OLA1 binds and hydrolyzes ATP as its primary substrate. Reason: This IBA annotation represents the core molecular function of OLA1. The phylogenetic inference is strongly validated by direct experimental evidence showing OLA1 defines an ATPase subfamily within the Obg family. Supporting Evidence: PMID:17430889 We have biochemically characterized the human homologue of YchF and found that it binds and hydrolyzes ATP more efficiently than GTP PMID:17430889 we have solved the x-ray structure of hOLA1 bound to the nonhydrolyzable ATP analogue AMPPCP |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | MODIFY | Summary: Keyword-based nucleotide binding annotation is accurate but overly general. OLA1 specifically binds ATP as its primary substrate. Reason: While OLA1 does bind nucleotides, this term is too broad. The protein has evolved specific ATP-binding preference over GTP. More specific ATP binding annotation exists. Proposed replacements: ATP binding Supporting Evidence: PMID:17430889 found that it binds and hydrolyzes ATP more efficiently than GTP |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: Combined methods correctly predict ATP binding, which is experimentally confirmed as OLA1's primary nucleotide substrate. Reason: This IEA annotation accurately captures OLA1's nucleotide specificity. Despite being in the Obg GTPase family, OLA1 has evolved to preferentially bind and hydrolyze ATP. Supporting Evidence: PMID:17430889 hOLA1 bound to the nonhydrolyzable ATP analogue AMPPCP |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro-based GTP binding prediction. The original review marked this REMOVE based on Koller-Eichhorn 2007. However, falcon deep research surfaces that OLA1 is an atypical NTPase that can bind and hydrolyze both ATP and GTP, with Chen et al. 2015 (PMID:26283179) actually reporting stronger GTPase than ATPase activity (Kcat 0.677/min vs 0.065/min) and Sidlowski 2023 (PMID:36481055) describing a phosphorylation-controlled switch where T325 phosphorylation increases GTPase activity. Action revised REMOVE -> KEEP_AS_NON_CORE. Reason: OLA1 does bind GTP in a regulated, phospho-state-dependent manner. ATP is the preferred substrate based on structural determinants (G4 motif NxxE, Koller-Eichhorn 2007), but GTP binding/hydrolysis is biologically relevant under phosphorylation control. Marked as non-core because ATPase activity is the predominant baseline function. Supporting Evidence: PMID:17430889 altered nucleotide specificity of YchF homologues and identify the Ola1/YchF subfamily of the Obg-related NTPases as an exceptional example of a single protein subfamily, which has evolved altered nucleotide specificity file:human/OLA1/OLA1-deep-research-falcon.md Dual ATP/GTP binding/hydrolysis: Reviews and primary work indicate OLA1/YchF can bind and hydrolyze both ATP and GTP, although multiple structural determinants bias human OLA1 toward ATP. file:human/OLA1/OLA1-deep-research-falcon.md ERK2 phosphorylation at Thr325 alters OLA1 biochemical behavior and DNA binding, with evidence that T325 phosphorylation increases GTPase activity and suppresses ATPase activity and potentiates DNA binding. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Subcellular location-based nuclear annotation. Baseline OLA1 is predominantly cytoplasmic, but Sidlowski et al. 2023 (PMID:36481055) demonstrated stress-induced nuclear translocation of OLA1 in pulmonary vascular cells. Phosphorylation at S232/Y236 by ERK1 triggers nuclear import via importin-alpha1 (KPNA2), and phospho-T325 OLA1 binds DNA and activates transcription of nuclear-encoded mitochondrial bioenergetic genes. Action revised REMOVE -> KEEP_AS_NON_CORE based on falcon deep research. Reason: Nuclear localization is now experimentally supported as a stress-induced, regulated state rather than baseline. It is not the predominant or core localization (which is cytosolic/mitochondrial), but Sidlowski 2023 establishes a real, regulated nuclear pool with a functional role in mitonuclear retrograde signaling. Marked as non-core rather than removed. Supporting Evidence: GO_REF:0000054 Gene Ontology annotation based on curation of intracellular localizations of expressed fusion proteins in living cells [shows cytoplasmic, not nuclear] file:human/OLA1/OLA1-deep-research-falcon.md ERK1 phosphorylation at Ser232/Tyr236 triggers OLA1 translocation from cytoplasm/mitochondria to nucleus. file:human/OLA1/OLA1-deep-research-falcon.md Stress-induced nuclear translocation: Cellular stresses (hypoxia, H2O2, mitochondrial uncoupling) induce nuclear accumulation of OLA1, with mechanistic dependence on ERK phosphorylation and nuclear import machinery (importin-alpha1) and the cytoskeletal intermediate filament vimentin. |
| GO:0005730 nucleolus | IEA GO_REF:0000120 | REMOVE | Summary: Combined methods predicting nucleolar localization lacks experimental validation. Reason: No experimental evidence supports nucleolar localization. OLA1's well-characterized functions with ribosomes, eIF2, and HSP70 occur in the cytoplasm. Supporting Evidence: GO_REF:0000052 Gene Ontology annotation based on curation of immunofluorescence data [shows cytosolic] |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Combined methods correctly predict cytoplasmic localization, consistent with experimental evidence. Reason: This IEA annotation is accurate and supported by multiple experimental approaches showing OLA1 is predominantly cytoplasmic. Supporting Evidence: GO_REF:0000054 Gene Ontology annotation based on curation of intracellular localizations of expressed fusion proteins in living cells |
| GO:0016787 hydrolase activity | IEA GO_REF:0000043 | MODIFY | Summary: Keyword-based hydrolase activity annotation is accurate but too general. Reason: While technically correct that OLA1 is a hydrolase, this term is too broad. The specific ATP hydrolysis activity better captures OLA1's molecular function. Proposed replacements: ATP hydrolysis activity Supporting Evidence: PMID:17430889 binds and hydrolyzes ATP more efficiently than GTP |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined methods correctly predict ATP hydrolysis activity, experimentally confirmed. Reason: This IEA annotation accurately identifies OLA1's core molecular function. Despite being computationally derived, it correctly captures the validated ATPase activity. Supporting Evidence: PMID:17430889 Human OLA1 defines an ATPase subfamily in the Obg family |
| GO:0043022 ribosome binding | IEA GO_REF:0000104 | ACCEPT | Summary: Sequence feature-based ribosome binding prediction is accurate. OLA1 binds to 80S ribosomes to regulate translation. Reason: This annotation correctly identifies a core function. OLA1 contains a TGS domain for RNA binding and binds ribosomes, with ribosomes stimulating its ATPase activity. Supporting Evidence: GO_REF:0000104 Electronic Gene Ontology annotations created by transferring manual GO annotations between related proteins based on shared sequence features |
| GO:0043023 ribosomal large subunit binding | IEA GO_REF:0000104 | ACCEPT | Summary: Sequence feature prediction of large subunit binding is supported by structural studies. Reason: Structural data shows bacterial YchF contacts the 50S ribosomal subunit. OLA1 binds at the ribosomal subunit interface to promote splitting during translation stalling. Supporting Evidence: GO_REF:0000104 Electronic Gene Ontology annotations created by transferring manual GO annotations between related proteins based on shared sequence features |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | ACCEPT | Summary: Keyword-based metal ion binding is likely correct as P-loop NTPases require metal ions. Reason: As an ATPase with Walker motifs, OLA1 requires metal ion coordination (typically Mg2+) for ATP binding and hydrolysis, standard for P-loop NTPases. Supporting Evidence: PMID:17430889 P-loop GTPases and related ATPases, which perform essential functions |
| GO:0005515 protein binding | IPI PMID:22190034 Global landscape of HIV-human protein complexes. | MODIFY | Summary: Physical interaction with HIV proteins detected by mass spectrometry. Generic protein binding term is uninformative. Reason: The term protein binding is too vague. OLA1 has specific interactions with eIF2, HSP70, BRCA1/BARD1, and ribosomes that should be annotated specifically. GO:0051082 unfolded protein binding was dropped from the proposed replacements because it is obsolete and OLA1 is not an unfolded-protein binder (the IPI partner here is an HIV Gag product). Proposed replacements: ribosome binding Supporting Evidence: PMID:22190034 497 HIV-human protein-protein interactions involving 435 individual human proteins |
| GO:0005813 centrosome | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence demonstrates centrosome localization, consistent with BRCA1/BARD1 interaction. Reason: Direct experimental evidence shows OLA1 localizes to centrosomes, where it interacts with BRCA1/BARD1 to regulate centrosome duplication. Supporting Evidence: GO_REF:0000052 Gene Ontology annotation based on curation of immunofluorescence data |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence confirms cytosolic localization, consistent with OLA1's primary functions. Reason: Direct experimental evidence supports cytosolic as the primary localization where OLA1 performs core functions including ribosome binding and HSP70 stabilization. Supporting Evidence: GO_REF:0000052 Gene Ontology annotation based on curation of immunofluorescence data |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | KEEP AS NON CORE | Summary: High-throughput proteomics identified OLA1 in E-cadherin complexes. This may represent a peripheral interaction. Reason: While OLA1 was detected in E-cadherin complexes by proteomics, this is not a core function. OLA1's primary roles are in translation regulation and stress responses. Supporting Evidence: PMID:25468996 E-cadherin interactome complexity and robustness resolved by quantitative proteomics |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-481007 | REMOVE | Summary: Reactome pathway annotation places OLA1 in platelet alpha granules released extracellularly. Supported by exosome proteomics. Reason: While OLA1 is detected in extracellular exosomes and platelet granules, there is no evidence it performs any functional role in the extracellular region. This is likely cellular export/disposal rather than a functional localization. Supporting Evidence: Reactome:R-HSA-481007 Exocytosis of platelet alpha granule contents |
| GO:0031093 platelet alpha granule lumen | TAS Reactome:R-HSA-481007 | REMOVE | Summary: Reactome annotation correctly places OLA1 in platelet alpha granule lumen for secretion. Reason: While OLA1 is detected in platelet alpha granules, there is no evidence it performs any function there. This appears to be a transport/secretion compartment rather than a functional localization. Supporting Evidence: Reactome:R-HSA-481007 Alpha granules contain mainly polypeptides such as fibrinogen, von Willebrand factor, growth factors |
| GO:0016887 ATP hydrolysis activity | IDA PMID:17430889 Human OLA1 defines an ATPase subfamily in the Obg family of ... | ACCEPT | Summary: Direct experimental demonstration that OLA1 hydrolyzes ATP more efficiently than GTP (Koller-Eichhorn 2007, PMID:17430889), with crystal structure solved. Note: Chen et al. 2015 (PMID:26283179) reported the opposite Kcat ratio with stronger GTPase activity; Sidlowski 2023 (PMID:36481055, surfaced by falcon) proposes a phosphorylation-controlled biochemical switch in which T325 phosphorylation increases GTPase and suppresses ATPase activity, potentially reconciling the conflicting in vitro measurements. Reason: Gold standard annotation - direct experimental evidence for OLA1's core molecular function. The study definitively established OLA1 as an ATPase. Supporting Evidence: PMID:17430889 We have biochemically characterized the human homologue of YchF and found that it binds and hydrolyzes ATP more efficiently than GTP file:human/OLA1/OLA1-deep-research-falcon.md ERK2 phosphorylation at Thr325 alters OLA1 biochemical behavior and DNA binding, with evidence that T325 phosphorylation increases GTPase activity and suppresses ATPase activity and potentiates DNA binding. |
| GO:0046034 ATP metabolic process | IDA PMID:17430889 Human OLA1 defines an ATPase subfamily in the Obg family of ... | ACCEPT | Summary: Direct experimental evidence for ATP metabolic process through OLA1's ATPase activity. Reason: OLA1's ATP hydrolysis activity directly participates in ATP metabolic processes. The experimental evidence clearly demonstrates ATP turnover. Supporting Evidence: PMID:17430889 binds and hydrolyzes ATP more efficiently than GTP. For this reason, we have termed the protein hOLA1, for human Obg-like ATPase 1 |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | REMOVE | Summary: High-throughput proteomics of NK cell membranes detected OLA1. This broad membrane annotation is imprecise. Reason: OLA1 lacks transmembrane domains and is not a membrane protein. Detection in membrane preparations likely reflects contamination or transient association. The annotation is misleading. Supporting Evidence: PMID:19946888 Defining the membrane proteome of NK cells |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | REMOVE | Summary: Large-scale proteomics identified OLA1 in urinary exosomes, confirming extracellular vesicle presence. Reason: Detection in exosomes does not indicate functional localization. No evidence suggests OLA1 performs any molecular function in exosomes. This likely represents cellular export or disposal of the protein. Supporting Evidence: PMID:19056867 LC-MS/MS to profile the proteome of human urinary exosomes. Overall, the analysis identified 1132 proteins unambiguously |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | REMOVE | Summary: Proteomics of B-cell exosomes identified OLA1 among 539 proteins, providing independent confirmation. Reason: Detection in B-cell exosomes does not indicate functional localization. No evidence suggests OLA1 performs any molecular function in exosomes. This likely represents cellular export rather than functional localization. Supporting Evidence: PMID:20458337 analyzed the total proteome of highly purified B cell-derived exosomes using sensitive and accurate mass spectrometry (MS), and identified 539 proteins |
| GO:0005737 cytoplasm | IDA GO_REF:0000054 | ACCEPT | Summary: GFP fusion protein studies directly demonstrate cytoplasmic localization. Reason: Direct experimental evidence using GFP fusion proteins shows OLA1 localizes to the cytoplasm, consistent with all characterized functions. Supporting Evidence: GO_REF:0000054 Gene Ontology annotation based on curation of intracellular localizations of expressed fusion proteins in living cells |
| GO:0005524 ATP binding | IDA PMID:17430889 Human OLA1 defines an ATPase subfamily in the Obg family of ... | ACCEPT | Summary: Crystal structure of hOLA1 bound to ATP analog AMPPCP provides direct structural evidence for ATP binding. Reason: Gold standard experimental evidence - crystal structure directly shows ATP binding. This study definitively established OLA1's nucleotide specificity for ATP. Supporting Evidence: PMID:17430889 To explain ATP specificity of hOLA1, we have solved the x-ray structure of hOLA1 bound to the nonhydrolyzable ATP analogue AMPPCP |
| GO:0031369 translation initiation factor binding | IPI PMID:26283179 OLA1 regulates protein synthesis and integrated stress respo... | NEW | Summary: OLA1 directly binds eIF2 to regulate translation initiation, interfering with eIF2 ternary-complex (TC) formation. Per PR #849 review feedback the evidence provenance was corrected: changed IBA + PMID:17430889 (an ATPase-characterization title that does not demonstrate eIF2 binding) to IPI + PMID:26283179 (Chen et al. 2015), which directly establishes the OLA1-eIF2 interaction. Reason: This critical molecular function is not captured in existing annotations but is well-supported by literature. OLA1's interaction with eIF2 is a core mechanism for translational control. Supporting Evidence: PMID:26283179 OLA1, a member of the ancient Obg family of GTPases, is an eIF2-regulatory protein that inhibits protein synthesis and promotes ISR by binding eIF2, hydrolyzing GTP, and interfering with TC formation file:human/OLA1/OLA1-deep-research-falcon.md Translation initiation machinery: OLA1 is reported to bind eIF2 and to inhibit translation initiation by preventing formation of the eIF2.GTP.Met-tRNAi ternary complex, thereby modulating pathways central to the integrated stress response (ISR). |
| GO:0030544 Hsp70 protein binding | TAS PMID:37109587 The Universally Conserved Unconventional G Protein YchF Is C... | NEW | Summary: OLA1/hOLA1 binds HSP70, interacting with the C-terminal variable domain of HSP70 to block CHIP contact and thereby stabilizing HSP70 (within the CHIP/HSP70/SOD2 proteostasis axis). Per PR #849 re-review feedback the evidence was upgraded from NAS (falcon synthesis) to TAS anchored on the Lin et al. 2023 review (PMID:37109587), which states authoritatively that hOLA1 interacts with the C-terminal variable domain of HSP70. Reason: OLA1's direct interaction with HSP70 (stabilization within the CHIP/HSP70/SOD2 proteostasis axis) supports a heat-shock/protein-quality- control role. Provenance now anchored on the Lin 2023 review (TAS). Supporting Evidence: PMID:37109587 hOLA1 interacts with the C-terminal variable domain of HSP70 to prevent contact with the C-terminus of Hsp70-binding protein (CHIP), an E3 ubiquitin ligase for HSP70, thereby inhibiting HSP70 from the CHIP-mediated ubiquitination. file:human/OLA1/OLA1-deep-research-falcon.md OLA1 has been linked to heat-shock resilience via **HSP70 stabilization** and to oxidative stress control through effects on the **CHIP/HSP70/SOD2** axis. |
| GO:0032790 ribosome disassembly | TAS file:human/OLA1/OLA1-deep-research.md | NEW | Summary: OLA1 promotes ribosome splitting when translation is stalled on D/E-rich sequences, acting as a ribosome rescue factor. Reason: Well-supported biological process not in GOA. OLA1/YchF promotes the splitting of ribosomes into subunits during translation stalling. Supporting Evidence: file:human/OLA1/OLA1-deep-research.md OLA1 promotes ribosome splitting when translation is stalled on D/E-rich sequences, acting as a ribosome rescue factor |
| GO:0140467 integrated stress response signaling | IDA PMID:26283179 OLA1 regulates protein synthesis and integrated stress respo... | NEW | Summary: OLA1 participates in the integrated stress response by regulating eIF2 function and translation initiation under stress. Per PR #849 review feedback, the original_reference_id was changed from the file: deep research ref to the primary publication PMID:26283179 (Chen et al. 2015) to match the IDA evidence type. Reason: OLA1 is a key player in ISR signaling through its interaction with eIF2 and regulation of translation during stress. Supporting Evidence: PMID:26283179 Depletion of OLA1 caused a hypoactive ISR and greater survival in stressed cells file:human/OLA1/OLA1-deep-research-falcon.md The Lin 2023 review summarizes that hOLA1 blocks ternary complex formation and thereby prevents eIF2 from delivering initiator tRNA to the 40S ribosome. file:human/OLA1/OLA1-deep-research-falcon.md The Lin 2023 review summarizes that hOLA1 blocks ternary complex formation and thereby prevents eIF2 from delivering initiator tRNA to the 40S ribosome. |
| GO:0006417 regulation of translation | TAS file:human/OLA1/OLA1-deep-research.md | NEW | Summary: OLA1 regulates translation through ribosome binding and control of translation initiation and elongation. Reason: Core biological process - OLA1 regulates both translation initiation (via eIF2) and elongation (via ribosome rescue). Supporting Evidence: file:human/OLA1/OLA1-deep-research.md OLA1 coordinates cellular responses to heat shock, oxidative stress, and DNA damage |
| GO:0045947 negative regulation of translational initiation | TAS file:human/OLA1/OLA1-deep-research.md | NEW | Summary: OLA1 negatively regulates translation initiation by binding eIF2 and preventing Met-tRNA loading. Reason: Specific mechanism of translation regulation - OLA1 acts as a brake on translation initiation under normal conditions. Supporting Evidence: file:human/OLA1/OLA1-deep-research.md OLA1 binding to eIF2 prevents eIF2 from assembling the translation pre-initiation complex PMID:26283179 OLA1 thus represents a novel mechanism of translational control affecting de novo TC formation, different from the traditional model in which phosphorylation of eIF2alpha blocks the regeneration of TC file:human/OLA1/OLA1-deep-research-falcon.md OLA1 binds eIF2 and stabilizes eIF2 in its GDP-bound state, inhibiting ternary complex formation and thereby decreasing canonical cap-dependent initiation while favoring stress-adaptive alternative initiation. |
| GO:0009408 response to heat | TAS file:human/OLA1/OLA1-deep-research.md | NEW | Summary: OLA1 plays a protective role during heat shock by stabilizing HSP70 levels. Reason: OLA1 is a positive regulator of heat shock response through HSP70 stabilization. Supporting Evidence: file:human/OLA1/OLA1-deep-research.md OLA1 plays a protective role during heat shock by stabilizing molecular chaperones |
| GO:0031397 negative regulation of protein ubiquitination | TAS file:human/OLA1/OLA1-deep-research.md | NEW | Summary: OLA1 prevents HSP70 ubiquitination by competing with CHIP E3 ligase for binding sites. Reason: Specific mechanism - OLA1 protects HSP70 from ubiquitination and degradation. Supporting Evidence: file:human/OLA1/OLA1-deep-research.md OLA1 protects HSP70 from ubiquitination and subsequent proteasomal degradation |
| GO:0010826 negative regulation of centrosome duplication | TAS file:human/OLA1/OLA1-deep-research.md | NEW | Summary: OLA1 regulates centrosome duplication through interaction with BRCA1/BARD1. Reason: Loss of OLA1 leads to centrosome amplification, indicating negative regulation of centrosome duplication. Supporting Evidence: file:human/OLA1/OLA1-deep-research.md perturbation of OLA1 is associated with centrosome amplification in cells |
| GO:0051301 cell division | TAS file:human/OLA1/OLA1-deep-research.md | NEW | Summary: OLA1 participates in cell division through centrosome regulation. Reason: OLA1 influences cell division through its role in centrosome dynamics and genomic stability. Supporting Evidence: file:human/OLA1/OLA1-deep-research.md OLA1, via binding BRCA1/BARD1, influences centrosome dynamics |
| GO:1902883 negative regulation of response to oxidative stress | IMP PMID:19706404 OLA1, an Obg-like ATPase, suppresses antioxidant response vi... | NEW | Summary: OLA1 functions as a negative regulator of the cellular antioxidant response. Per PR #849 re-review feedback, the evidence_type was changed from IDA to IMP because PMID:19706404 (Zhang et al. 2009, "OLA1, an Obg-like ATPase, suppresses antioxidant response via nontranscriptional mechanisms") supports this via overexpression/knockdown phenotypes (a mutant/altered-gene-product phenotype), which is IMP evidence rather than a direct assay (IDA). Reason: OLA1 depletion enhances oxidative stress resistance, demonstrating negative regulation of stress response. Supporting Evidence: PMID:19706404 overexpression of OLA1 increased cellular sensitivity to tBH and diamide. file:human/OLA1/OLA1-deep-research-falcon.md OLA1 has long-standing links to oxidative stress regulation, including suppressing antioxidant responses via nontranscriptional mechanisms and influencing mitochondrial antioxidant enzyme status (SOD2), with downstream implications for cellular stress tolerance. file:human/OLA1/OLA1-deep-research-falcon.md OLA1 has long-standing links to oxidative stress regulation, including suppressing antioxidant responses via nontranscriptional mechanisms and influencing mitochondrial antioxidant enzyme status (SOD2), with downstream implications for cellular stress tolerance. |
| GO:0005741 mitochondrial outer membrane | IDA PMID:36481055 OLA1 Phosphorylation Governs the Mitochondrial Bioenergetic ... | NEW | Summary: Sidlowski 2023 (PMID:36481055), surfaced by falcon deep research, reports that OLA1 in pulmonary vascular cells shows a strong mitochondrial pool and localizes to the outer mitochondrial membrane, supported by biochemical fractionation, protease protection, and marker co-staining. The mitochondrial pool is anchored by vimentin and relocates to the nucleus under stress. Reason: Falcon deep research surfaces a previously uncaptured mitochondrial outer membrane localization with direct experimental support (biochemical fractionation and protease protection). This is a real, regulated localization that participates in the OLA1 stress-response cycle. Supporting Evidence: file:human/OLA1/OLA1-deep-research-falcon.md Mitochondrial localization: In pulmonary vascular cells, OLA1 shows a strong mitochondrial pool and is reported to localize to the outer mitochondrial membrane (supported by biochemical fractionation/protease protection and marker co-staining). PMID:36481055 OLA1 phosphorylation at Ser232/Tyr236 triggers its translocation from the cytoplasm and mitochondria into the nucleus |
| GO:0140053 mitochondrial gene expression | IMP PMID:36481055 OLA1 Phosphorylation Governs the Mitochondrial Bioenergetic ... | NEW | Summary: Sidlowski 2023 (PMID:36481055) showed that nuclear OLA1 (phospho-T325) regulates expression of nuclear-encoded mitochondrial genes involved in oxidative phosphorylation and mitochondrial assembly. OLA1 depletion downregulates these genes; phosphomimetic T325D rescues expression better than phosphoresistant T325A. This is a mitonuclear retrograde signaling role. Reason: Falcon deep research surfaces this newer mechanism: stress -> ERK1/2 phosphorylation -> OLA1 nuclear relocation -> altered DNA binding and transcriptional activation of nuclear-encoded mitochondrial genes, with functional consequences for cellular bioenergetics. Supporting Evidence: file:human/OLA1/OLA1-deep-research-falcon.md OLA1 depletion downregulates nuclear genes involved in oxidative phosphorylation and mitochondrial assembly/structure; phosphomimetic nuclear OLA1 (T325D) rescues mitochondrial gene expression better than phosphoresistant T325A. PMID:36481055 human OLA1 (Obg-like ATPase-1) couples redox signals to the metabolic response pathway by activating metabolic gene transcription in the nucleus |
| GO:0007005 mitochondrion organization | IMP PMID:36481055 OLA1 Phosphorylation Governs the Mitochondrial Bioenergetic ... | NEW | Summary: Sidlowski 2023 (PMID:36481055) found that lungs of OLA1 knockout mice have fewer mitochondria, lower cellular ATP, and higher lactate, indicating a role in mitochondrial biogenesis/maintenance via regulation of nuclear-encoded mitochondrial bioenergetic genes. Reason: Direct loss-of-function phenotype: OLA1 deletion reduces mitochondrial content and impairs bioenergetic function, supporting a role in regulating mitochondrion organization downstream of the mitonuclear retrograde signaling axis. Supporting Evidence: PMID:36481055 the lungs of OLA1 knockout mice have fewer mitochondria, lower cellular ATP concentrations, and higher lactate concentrations file:human/OLA1/OLA1-deep-research-falcon.md Functional metabolic outcomes include lower cellular ATP, higher lactate, and increased ADP:ATP ratio in OLA1-deficient endothelial cells. |
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)