Affinage

Showing NDUFA13 — GRIM-19 is a alias.

NDUFA13

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 · UniProt Q9P0J0

Length
144 aa
Mass
16.7 kDa
Annotated
2026-06-10
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NDUFA13/GRIM-19 is an essential accessory subunit of the hydrophilic arm of mitochondrial NADH:ubiquinone oxidoreductase (complex I) that couples respiratory chain bioenergetics to apoptotic and inflammatory signaling (PMID:11522775, PMID:15367666). As a structural subunit it is required for complex I assembly, electron transfer activity, and maintenance of the mitochondrial membrane potential, with its N-terminal sequence providing the mitochondrial localization signal and its C-terminal region required for both assembly into complex I and membrane potential maintenance; its loss destabilizes complex I holoenzyme and supercomplexes and is embryonic-lethal in mice (PMID:15367666, PMID:18287540, PMID:25901006). A germline pathogenic NDUFA13 mutation causes an isolated complex I deficiency in patients, with reduced NDUFA13 protein, complex I, and supercomplexes (PMID:25901006). Beyond bioenergetics, GRIM-19 was identified as a mediator of IFN-β/retinoic acid-induced tumor cell death (PMID:10924506) and functions as a specific inhibitor of STAT3: it binds STAT3 (but not STAT1 or STAT5a) through a structural motif in its N-terminus that engages the STAT3 transactivation domain in an S727-dependent manner, blocking STAT3 nuclear translocation and transcriptional activity without preventing STAT3 activation or DNA binding (PMID:12628925, PMID:12867595, PMID:20595633). It also acts as a chaperone recruiting STAT3 into the inner mitochondrial membrane via Tom20 and integrating it into complex I (PMID:23271731, PMID:39643607). Through these activities GRIM-19 functions as a tumor suppressor: monoallelic loss promotes STAT3-driven carcinogenesis, and tumor-derived N-terminal mutations (L71P, L91P, A95T) selectively abrogate STAT3 binding and anti-oncogenic functions (PMID:23386605, PMID:24145455). GRIM-19 additionally couples complex I-dependent mitochondrial ROS to innate immunity, being required for NLRP3 inflammasome/caspase-1/IL-1β activation and bactericidal macrophage function (PMID:22665480, PMID:34907600), and engages partners including HtrA2 (augmenting XIAP degradation) and NOD2 (enabling NF-κB activation) (PMID:15753091, PMID:17297443). Multiple viral oncoproteins (KSHV vIRF1, HPV16 E6, HHV-6B U95) target GRIM-19 to subvert its apoptotic and bioenergetic functions (PMID:12163600, PMID:17928352, PMID:21765936).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2000 Medium

    Before any molecular role was known, a functional screen established GRIM-19 as a required mediator of cytokine-induced tumor cell death, framing it as a candidate cell-death effector rather than a housekeeping protein.

    Evidence Antisense cDNA knockout genetic screen with overexpression and survival validation in IFN-β/retinoic acid-treated tumor cells

    PMID:10924506

    Open questions at the time
    • Did not identify the biochemical activity underlying death induction
    • Initial nuclear localization claim not reconciled with later mitochondrial assignment
  2. 2001 High

    Direct biochemical identification placed GRIM-19 in the respiratory machinery, establishing it as a bona fide complex I subunit in the hydrophilic arm.

    Evidence Mass spectrometric sequencing of purified bovine complex I subcomplex Iλ plus cDNA cloning and intact mass measurement

    PMID:11522775

    Open questions at the time
    • Did not test whether the subunit is required for assembly or activity
    • Connection to the death phenotype not yet made
  3. 2003 High

    Two independent studies converged to define GRIM-19 as a specific STAT3 inhibitor, mapping the interaction to the STAT3 transactivation domain and S727 and showing repression of transcription without blocking activation or DNA binding.

    Evidence Yeast two-hybrid, reciprocal co-immunoprecipitation, domain/point mutagenesis, reporter assays, EMSA and confocal imaging across multiple cell types

    PMID:12628925 PMID:12867595

    Open questions at the time
    • Did not establish how a complex I subunit accesses STAT3
    • Structural basis of the S727-dependent interaction not resolved
  4. 2004 High

    Knockout demonstrated GRIM-19 is indispensable for complex I assembly and electron transfer and for embryonic viability, proving its bioenergetic role is essential rather than accessory.

    Evidence Gene-targeted knockout mouse (E9.5 lethality), blue native PAGE, native activity assays, and EM of blastocyst mitochondria

    PMID:15367666

    Open questions at the time
    • Did not separate bioenergetic from STAT3-regulatory contributions to phenotype
    • Mechanism of assembly support not defined
  5. 2008 High

    Domain dissection separated GRIM-19's assembly role from membrane-potential maintenance, localizing the mitochondrial targeting signal to the N-terminus and identifying regions whose loss abolishes ΔΨm and sensitizes cells to apoptosis.

    Evidence Systematic deletion/truncation/point mutagenesis with JC-1 ΔΨm readout, blue native PAGE, and apoptosis assays including a dominant-negative mutant

    PMID:18287540

    Open questions at the time
    • Did not define the molecular basis by which the C-terminal region maintains ΔΨm
    • Did not link ΔΨm maintenance to specific downstream signaling
  6. 2012 High

    Reconstituted import showed GRIM-19 chaperones STAT3 into the inner mitochondrial membrane and complex I, providing the physical mechanism by which the two interacting proteins co-reside in mitochondria.

    Evidence In vitro mitochondrial import assay, inner-membrane fractionation, blue native PAGE, and S727A STAT3 mutagenesis

    PMID:23271731

    Open questions at the time
    • Functional consequence of mitochondrial STAT3 on complex I activity not quantified
    • Import receptor not identified in this study
  7. 2012 Medium

    GRIM-19 was placed in a death-signaling axis in which RIPK1-dependent S727 phosphorylation drives STAT3-GRIM-19 association, mitochondrial STAT3 translocation, and ROS-dependent necroptosis.

    Evidence Co-IP conditioned on phosphorylation, RIPK1 knockdown/necrostatin-1, mitochondrial fractionation, ROS and viability assays

    PMID:22393233

    Open questions at the time
    • Single lab; reciprocal validation of the phospho-dependent interaction limited
    • Source of mitochondrial ROS not mechanistically isolated
  8. 2012 High

    A heterozygous knockout linked GRIM-19 dosage to innate immune competence, connecting reduced complex I activity and elevated macrophage ROS to defective bacterial killing and cytokine output.

    Evidence GRIM-19+/− mouse macrophages with complex I activity, ROS, bacterial killing, phagosome-lysosome fusion, and cytokine ELISA assays

    PMID:22665480

    Open questions at the time
    • Did not define the downstream inflammasome step linking ROS to cytokines
    • Did not separate STAT3-dependent from bioenergetic contributions
  9. 2013 High

    In vivo and patient-derived genetics established GRIM-19 as a haploinsufficient tumor suppressor, with monoallelic loss promoting STAT3-driven carcinogenesis and tumor-derived N-terminal mutations selectively crippling STAT3 binding and anti-oncogenic function.

    Evidence Conditional skin knockout with chemical carcinogenesis, tumor sequencing of L71P/L91P/A95T mutants, co-IP, reporter, transformation and metastasis assays

    PMID:23386605 PMID:24145455

    Open questions at the time
    • Relative contribution of ETC dysfunction versus STAT3 derepression to tumorigenesis not resolved
    • Whether mutations affect bioenergetic function not addressed
  10. 2022 High

    CRISPR knockout positioned GRIM-19 upstream of the NLRP3 inflammasome, showing it is required for mitochondrial ROS generation, caspase-1 activation, and IL-1β production, and that the mycobacterial protease Zmp1 targets it.

    Evidence CRISPR/Cas9 macrophage knockout with IL-1β ELISA, caspase-1 activity, mitochondrial ROS and ΔΨm assays, and Zmp1 overexpression

    PMID:34907600

    Open questions at the time
    • Direct physical link between GRIM-19/complex I ROS and NLRP3 not structurally defined
    • Whether Zmp1 binding disrupts complex I or STAT3 functions untested
  11. 2024 Medium

    GRIM-19 was shown to recruit STAT3 to mitochondria via the import receptor Tom20 and to induce mitophagy in a fibrosis model, refining the chaperone mechanism with a named receptor.

    Evidence Overexpression in a murine systemic sclerosis model, Tom20 co-IP, mitochondrial STAT3 quantification, and mitophagy assays

    PMID:39643607

    Open questions at the time
    • Single lab; reciprocal Tom20 validation limited
    • Link between mitoSTAT3 recruitment and mitophagy induction mechanistically incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GRIM-19's structural role in complex I, its STAT3-sequestering activity, and its control of mitochondrial ROS are quantitatively partitioned across bioenergetic, apoptotic, and inflammatory outcomes remains unresolved.
  • No structure of the GRIM-19–STAT3 interface
  • Causal hierarchy between complex I dysfunction and each downstream signaling branch not established
  • Whether disease and tumor mutations act primarily through STAT3 or bioenergetics undetermined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0016491 oxidoreductase activity 3 GO:0098772 molecular function regulator activity 3 GO:0044183 protein folding chaperone 2
Localization
GO:0005739 mitochondrion 3
Pathway
R-HSA-5357801 Programmed Cell Death 3 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 2
Partners
BCL2L1HTRA2NOD2STAT3TOMM20UBE3A
Complex memberships
mitochondrial respiratory chain complex I

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 NDUFA13/GRIM-19 was identified as a bona fide subunit of bovine mitochondrial NADH:ubiquinone oxidoreductase (complex I), specifically residing in the hydrophilic arm (subcomplex Iλ). The intact protein is N-terminally acetylated. Denaturing gel electrophoresis of purified complex I subcomplex, tryptic digestion, mass spectrometric peptide sequencing, cDNA cloning, intact protein mass measurement The Journal of biological chemistry High 11522775
2000 GRIM-19 is required for IFN-β/retinoic acid-induced tumor cell death; antisense ablation confers resistance to this death stimulus, and overexpression enhances cell death. The protein was initially characterized as a nuclear protein whose expression is induced by the IFN/RA combination. Antisense cDNA knockout genetic screen, antisense overexpression survival assay, overexpression cell death assay The Journal of biological chemistry Medium 10924506
2003 GRIM-19 physically interacts specifically with STAT3 (but not STAT1 or STAT5a) via yeast two-hybrid and co-immunoprecipitation in multiple cell types. GRIM-19 co-localizes with mitochondrial markers, forms perinuclear aggregates with co-expressed STAT3, inhibits STAT3 nuclear translocation stimulated by EGF, and represses STAT3 transcriptional activity and target gene expression. Yeast two-hybrid screen, co-immunoprecipitation, domain mapping, confocal microscopy co-localization, reporter gene assay, cell growth suppression assay The EMBO journal High 12628925
2003 GRIM-19 binds STAT3 and inhibits its transcriptional activity without blocking ligand-induced STAT3 activation or DNA binding. Mutational analysis showed that the transactivation domain of STAT3, especially residue S727, is required for GRIM-19 binding. GRIM-19 does not inhibit STAT1. Yeast two-hybrid screen, co-immunoprecipitation, mutational analysis, transcription reporter assays, EMSA Proceedings of the National Academy of Sciences of the United States of America High 12867595
2004 GRIM-19 is essential for mitochondrial complex I assembly and electron transfer activity. GRIM-19 knockout mice die at embryonic day 9.5, and GRIM-19−/− blastocysts show abnormal mitochondrial structure, morphology, and distribution. Deletion of GRIM-19 destroys complex I assembly and electron transfer activity and influences other respiratory chain complexes. Gene targeting/knockout mouse generation, native complex I activity assays, electron microscopy of mitochondria, blue native PAGE for complex assembly Molecular and cellular biology High 15367666
2008 GRIM-19 is required for maintenance of mitochondrial membrane potential (ΔΨm). Domain dissection showed the N-terminal sequence contains the mitochondrial localization signal, and deletions of residues 70–80, 90–100, or the entire C-terminal region (70–144) abolished ΔΨm without this effect being shared by other complex I subunits (NDUFA9, NDUFS3). Deletion of the last 10 residues prevented assembly into complex I. A dominant-negative mutant (N-terminal 60 aa + last 10 aa C-terminal) assembled into complex I but failed to maintain ΔΨm and sensitized cells to apoptosis. Deletion/truncation/point mutagenesis, mitochondrial membrane potential assays (JC-1), blue native PAGE for complex I assembly, apoptosis assays Molecular biology of the cell High 18287540
2002 KSHV vIRF1 directly interacts with GRIM-19 via its N-terminal region, colocalizes with GRIM-19 in cells, and deregulates GRIM-19-induced apoptosis, conferring resistance to IFN/RA-induced cell death. HPV16 E6 also binds GRIM-19. Yeast two-hybrid assay, co-immunoprecipitation in vivo, in vitro binding assay, confocal colocalization, cell death assay Journal of virology Medium 12163600
2005 GRIM-19 interacts with NOD2 in intestinal epithelial cells (HT29) and is required for NF-κB activation downstream of NOD2-mediated recognition of muramyl dipeptide (MDP). GRIM-19 also controls pathogen invasion of intestinal epithelial cells. Yeast two-hybrid screen, co-immunoprecipitation with endogenous NOD2, NF-κB reporter assay, bacterial invasion assay The Journal of biological chemistry Medium 15753091
2007 GRIM-19 physically interacts with the mitochondrial serine protease HtrA2, augments HtrA2-driven destruction of the antiapoptotic protein XIAP in an IFN/RA-dependent manner, and promotes cell death. The KSHV oncoprotein vIRF1 disrupts this GRIM-19–HtrA2 interaction. Yeast two-hybrid screen, co-immunoprecipitation, XIAP degradation assay, cell death assay Oncogene Medium 17297443
2007 GRIM-19 suppresses v-Src-induced oncogenic transformation by down-regulating STAT3-dependent gene expression and also inhibits src-induced tyrosyl phosphorylation of focal adhesion kinase (FAK), paxillin, E-cadherin, and γ-catenin independently of STAT3. Overexpression and shRNA knockdown, in vitro transformation assays, in vivo tumor xenografts, phosphotyrosine immunoblotting The American journal of pathology Medium 17823279
2007 The HHV-6B U95 immediate-early protein interacts with GRIM-19. This interaction was verified by Co-IP and confocal coimmunolocalization. Silencing U95 by RNAi reduced viral load and abrogated the loss of mitochondrial membrane potential caused by HHV-6B infection. Yeast two-hybrid screening, co-immunoprecipitation, confocal microscopy co-localization, RNA interference knockdown, mitochondrial membrane potential assay Journal of virology Medium 17928352
2009 GRIM-19 inhibits v-Src-induced cell motility by suppressing podosome formation (cytoskeletal remodeling). The N-terminus of GRIM-19 is critical for this function. Tumor-associated GRIM-19 mutations disrupted inhibition of cell motility independently of STAT3. Overexpression of wild-type and mutant GRIM-19, podosome/actin imaging, cell motility assays, in vivo metastasis assay Oncogene Medium 19151760
2012 GRIM-19 acts as a chaperone to recruit STAT3 into mitochondria, where STAT3 resides in the inner mitochondrial membrane. In vitro import assays showed GRIM-19 enhances integration of STAT3 into complex I. The S727A mutation in STAT3 reduces its import and assembly even in the presence of GRIM-19. In vitro mitochondrial import assay, mitochondrial fractionation (inner membrane localization), blue native PAGE for complex I assembly, S727A STAT3 mutagenesis The Journal of biological chemistry High 23271731
2012 During TNF-induced necroptosis, RIPK1-dependent phosphorylation of STAT3 on serine 727 induces STAT3 interaction with GRIM-19, leading to translocation of STAT3 to mitochondria, increased mitochondrial ROS production, and cell death. Co-immunoprecipitation, RIPK1 knockdown/necrostatin-1 inhibition, mitochondrial fractionation, ROS measurement, cell viability assay Journal of cell science Medium 22393233
2012 GRIM-19 heterozygous knockout mice have compromised complex I activity and increased ROS in macrophages. Bacterial infection induces rapid upregulation of GRIM-19 and complex I activity in wild-type macrophages; GRIM-19+/− macrophages have decreased intracellular bacterial killing (defect in phagosome-lysosome fusion) and reduced proinflammatory cytokine production (IL-1, IL-12, IL-6, IFN-γ). Heterozygous knockout mouse, complex I activity assay, ROS measurement, bacterial killing assay, phagosome fusion assay, ELISA for cytokines The Journal of biological chemistry High 22665480
2011 GRIM-19 disrupts the HPV E6/E6AP complex by physically interacting (via its N-terminus) with both E6 and E6AP; GRIM-19 promotes E6AP ubiquitination and degradation, thereby protecting p53 from E6-mediated degradation and inducing apoptosis in cervical cancer cells. Co-immunoprecipitation, GST pull-down assay, competition pull-down, in vivo and in vitro ubiquitination assay, xenograft mouse model PloS one Medium 21765936
2013 Tumor-derived somatic mutations in GRIM-19 (L71P, L91P, A95T) significantly impair GRIM-19's ability to associate with STAT3, block gene expression, suppress cellular transformation, and prevent metastasis in head and neck tumors. Tumor sequencing, co-immunoprecipitation with mutants, reporter assays, in vitro transformation assay, in vivo tumor growth and metastasis assays The Journal of biological chemistry Medium 23386605
2013 Monoallelic (heterozygous) loss of GRIM-19 in mouse skin promotes chemical carcinogenesis and formation of invasive squamous cell carcinomas, with high Stat3 activity, increased Stat3-responsive gene expression, mitochondrial electron transport dysfunction, failure to assemble ETC complexes, and altered glycolytic gene expression. Conditional skin-specific knockout mouse, chemical carcinogenesis protocol, blue native PAGE for ETC assembly, STAT3 reporter assay, metabolic gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 24145455
2013 GRIM-19 downregulation in glioblastoma promotes HIF1α accumulation in a STAT3-dependent manner; GRIM-19 loss allows STAT3 to act as a competitive inhibitor of pVHL–HIF1α interaction, preventing pVHL-mediated ubiquitination and proteasomal degradation of HIF1α, thereby promoting metabolic reprogramming toward glycolysis. shRNA knockdown, overexpression, co-immunoprecipitation (STAT3–pVHL–HIF1α), proteasome inhibitor treatment, HIF1α stability assay, metabolic assays Carcinogenesis Medium 23580587
2015 A germline pathogenic mutation in NDUFA13/GRIM-19 causes drastic reduction in complex I enzymatic activity in patient muscle biopsies and decreased complex I-driven respiration in fibroblasts (with preserved complex II, III, IV activities). Western blots showed decreased NDUFA13 protein, complex I holoenzyme, and supercomplexes in mitochondrial fractions. Silencing NDUFA13 in control cells reproduced the complex I instability. Next-generation sequencing, complex I enzymatic activity assay, oxygen consumption in fibroblasts, blue native PAGE/western blot for complex I and supercomplexes, siRNA knockdown in control cells Human molecular genetics High 25901006
2017 Cardiac-specific heterozygous knockout of NDUFA13 in mice yields normal cardiac function at baseline but resistance to ischemia-reperfusion injury. At basal state, cHet mice exhibit higher cytosolic H2O2 (but not mitochondrial). This H2O2 acts as a second messenger driving STAT3 dimerization and antiapoptotic signaling, resulting in suppressed superoxide burst and decreased infarct size during I/R. Cardiac-specific tamoxifen-inducible NDUFA13 KO mouse, I/R model, oxygen consumption rate assay, H2O2 measurement (cytosolic vs mitochondrial), STAT3 dimerization assay, infarct size measurement Proceedings of the National Academy of Sciences of the United States of America High 29078279
2021 GRIM-19 induces apoptosis in colorectal cancer cells in a p53-dependent manner via the SIRT7/PCAF/MDM2 axis: GRIM-19 activates SIRT7, which triggers PCAF-mediated ubiquitination of MDM2, stabilizing p53 protein. Overexpression/knockdown, co-immunoprecipitation, ubiquitination assay, flow cytometry for apoptosis, in vivo xenograft Experimental cell research Medium 34461110
2018 GRIM19 co-localizes with Bcl-xL in the mitochondria of bladder cancer cells. GRIM19 overexpression promotes Bcl-xL polyubiquitination and degradation via p38-MAPK and JNK pathways, contributing to cisplatin sensitization; inhibition of Bcl-xL rescues GRIM19 deficiency-caused cisplatin resistance. Co-immunoprecipitation, confocal colocalization, ubiquitination assay, kinase inhibitor experiments (p38/JNK), stable GRIM19 knockdown cell lines, xenograft mouse model Cancer chemotherapy and pharmacology Medium 30032449
2022 GRIM-19/NDUFA13 is a binding partner of mycobacterial Zmp1 metalloprotease. GRIM-19 is required for NLRP3 inflammasome activation: CRISPR/Cas9 knockout of GRIM-19 in macrophages abolishes IL-1β production in response to mycobacterial infection and to NLRP3 activators (ATP, nigericin). GRIM-19 is required for mitochondrial ROS generation and NLRP3-dependent caspase-1 activation. Forced Zmp1 expression or GRIM-19 loss decreases mitochondrial membrane potential. CRISPR/Cas9 knockout macrophage line, IL-1β ELISA, caspase-1 activity assay, mitochondrial ROS measurement, mitochondrial membrane potential assay, Zmp1 overexpression FASEB journal High 34907600
2020 GRIM-19 deficiency in gastric cancer cells triggers ROS-dependent activation of the NRF2-HO-1 axis, which drives metastasis. HO-1 inhibition reverses both GRIM-19 deficiency-driven NRF2 activation and NRF2 activator-induced NRF2 signaling via a positive-feedback NRF2-HO-1 loop. CRISPR/Cas9 lentivirus gene editing, in vivo metastasis mouse models, ROS inhibitor/NRF2 inhibitor/HO-1 inhibitor pharmacological intervention, reporter gene assay, flow cytometry Gastric cancer Medium 32770429
2010 A structural motif in the N-terminus of GRIM-19 is required for its interaction with STAT3 and antitumor activity; disruption of specific amino acids within this motif (including a clinically observed mutation) weakens STAT3 binding and abolishes growth-suppressive function. Mutational analysis, co-immunoprecipitation, reporter assays, transformation assays The American journal of pathology Medium 20595633
2016 GRIM-19 knockdown in Jurkat cells increases intracellular ROS and p-mTOR expression; NAC (ROS inhibitor) reverses p-mTOR upregulation from GRIM-19 loss, placing GRIM-19 upstream of a ROS–mTOR signaling axis that regulates Treg/Th17 balance. siRNA knockdown, intracellular ROS measurement (DCFH-DA), western blot for p-mTOR, NAC rescue experiment Molecular human reproduction Low 29741731
2024 GRIM-19 overexpression increases mitochondrial STAT3 (mitoSTAT3) levels, induces mitophagy, and alleviates fibrosis in an SSc model. GRIM-19 directly binds STAT3 and recruits it to mitochondria via the mitochondrial importer Tom20. Overexpression in murine SSc model, mitochondrial STAT3 quantification, mitophagy assay, Tom20 co-immunoprecipitation, in vivo bleomycin SSc model Experimental & molecular medicine Medium 39643607

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 GRIM-19, a cell death regulatory gene product, is a subunit of bovine mitochondrial NADH:ubiquinone oxidoreductase (complex I). The Journal of biological chemistry 205 11522775
2003 GRIM-19, a death-regulatory gene product, suppresses Stat3 activity via functional interaction. The EMBO journal 197 12628925
2012 The import of the transcription factor STAT3 into mitochondria depends on GRIM-19, a component of the electron transport chain. The Journal of biological chemistry 184 23271731
2000 Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-beta and retinoic acid combination, using a genetic approach. The Journal of biological chemistry 182 10924506
2004 GRIM-19, a cell death regulatory protein, is essential for assembly and function of mitochondrial complex I. Molecular and cellular biology 177 15367666
2005 Somatic and germline mutation in GRIM-19, a dual function gene involved in mitochondrial metabolism and cell death, is linked to mitochondrion-rich (Hurthle cell) tumours of the thyroid. British journal of cancer 159 15841082
2003 The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3. Proceedings of the National Academy of Sciences of the United States of America 150 12867595
2005 GRIM-19 interacts with nucleotide oligomerization domain 2 and serves as downstream effector of anti-bacterial function in intestinal epithelial cells. The Journal of biological chemistry 112 15753091
2012 GRIM-19-mediated translocation of STAT3 to mitochondria is necessary for TNF-induced necroptosis. Journal of cell science 91 22393233
2008 Effects of plasmid-based Stat3-specific short hairpin RNA and GRIM-19 on PC-3M tumor cell growth. Clinical cancer research : an official journal of the American Association for Cancer Research 83 18223232
2006 A proteomic analysis reveals the loss of expression of the cell death regulatory gene GRIM-19 in human renal cell carcinomas. Oncogene 81 16732315
2008 GRIM-19 is essential for maintenance of mitochondrial membrane potential. Molecular biology of the cell 78 18287540
2002 Viral interferon regulatory factor 1 of Kaposi's sarcoma-associated herpesvirus interacts with a cell death regulator, GRIM19, and inhibits interferon/retinoic acid-induced cell death. Journal of virology 70 12163600
2017 Electron leak from NDUFA13 within mitochondrial complex I attenuates ischemia-reperfusion injury via dimerized STAT3. Proceedings of the National Academy of Sciences of the United States of America 51 29078279
2018 GRIM-19 repressed hypoxia-induced invasion and EMT of colorectal cancer by repressing autophagy through inactivation of STAT3/HIF-1α signaling axis. Journal of cellular physiology 48 30537081
2010 Upregulation of the GRIM-19 gene suppresses invasion and metastasis of human gastric cancer SGC-7901 cell line. Experimental cell research 45 20478305
2015 Mutation in NDUFA13/GRIM19 leads to early onset hypotonia, dyskinesia and sensorial deficiencies, and mitochondrial complex I instability. Human molecular genetics 44 25901006
2012 Function of GRIM-19, a mitochondrial respiratory chain complex I protein, in innate immunity. The Journal of biological chemistry 40 22665480
2007 Tumor-suppressive activity of the cell death activator GRIM-19 on a constitutively active signal transducer and activator of transcription 3. Cancer research 39 17616678
2007 GRIM-19 associates with the serine protease HtrA2 for promoting cell death. Oncogene 36 17297443
2016 GRIM-19: A master regulator of cytokine induced tumor suppression, metastasis and energy metabolism. Cytokine & growth factor reviews 34 27659873
2013 Monoallelic loss of tumor suppressor GRIM-19 promotes tumorigenesis in mice. Proceedings of the National Academy of Sciences of the United States of America 34 24145455
2020 Mitochondrial GRIM-19 deficiency facilitates gastric cancer metastasis through oncogenic ROS-NRF2-HO-1 axis via a NRF2-HO-1 loop. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 33 32770429
2000 Chromosomal localization of human GRIM-19, a novel IFN-beta and retinoic acid-activated regulator of cell death. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 33 10926209
2018 Inhibition of miR-423-5p suppressed prostate cancer through targeting GRIM-19. Gene 32 30415005
2010 Overexpression of GRIM-19 in cancer cells suppresses STAT3-mediated signal transduction and cancer growth. Molecular cancer therapeutics 32 20682646
2020 Metformin protects high glucose‑cultured cardiomyocytes from oxidative stress by promoting NDUFA13 expression and mitochondrial biogenesis via the AMPK signaling pathway. Molecular medicine reports 29 33174032
2013 GRIM-19 opposes reprogramming of glioblastoma cell metabolism via HIF1α destabilization. Carcinogenesis 29 23580587
2012 Depletion of GRIM-19 accelerates hepatocellular carcinoma invasion via inducing EMT and loss of contact inhibition. Journal of cellular physiology 28 22105514
2011 Downregulation of GRIM-19 promotes growth and migration of human glioma cells. Cancer science 28 21827581
2016 Expression of GRIM-19 in adenomyosis and its possible role in pathogenesis. Fertility and sterility 27 26769301
2012 Downregulation of GRIM-19 is associated with hyperactivation of p-STAT3 in hepatocellular carcinoma. Medical oncology (Northwood, London, England) 27 22492280
2013 Tumor-derived mutations in the gene associated with retinoid interferon-induced mortality (GRIM-19) disrupt its anti-signal transducer and activator of transcription 3 (STAT3) activity and promote oncogenesis. The Journal of biological chemistry 26 23386605
2011 GRIM-19 function in cancer development. Mitochondrion 26 21664299
2007 Tumor suppressive protein gene associated with retinoid-interferon-induced mortality (GRIM)-19 inhibits src-induced oncogenic transformation at multiple levels. The American journal of pathology 26 17823279
2015 Decreased expression of GRIM-19 by DNA hypermethylation promotes aerobic glycolysis and cell proliferation in head and neck squamous cell carcinoma. Oncotarget 25 25575809
2007 The U95 protein of human herpesvirus 6B interacts with human GRIM-19: silencing of U95 expression reduces viral load and abrogates loss of mitochondrial membrane potential. Journal of virology 25 17928352
2002 Characterization of monoclonal antibodies against GRIM-19, a novel IFN-beta and retinoic acid-activated regulator of cell death. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 25 12433281
2019 OLFM4 Enhances STAT3 Activation and Promotes Tumor Progression by Inhibiting GRIM19 Expression in Human Hepatocellular Carcinoma. Hepatology communications 24 31304451
2012 GRIM-19 inhibits the STAT3 signaling pathway and sensitizes gastric cancer cells to radiation. Gene 24 23124042
2014 Expression of GRIM-19 in missed abortion and possible pathogenesis. Fertility and sterility 23 25455534
2013 Down-regulation of GRIM-19 is associated with STAT3 overexpression in breast carcinomas. Human pathology 23 23618357
2023 Mitochondrial GRIM-19 loss in parietal cells promotes spasmolytic polypeptide-expressing metaplasia through NLR family pyrin domain-containing 3 (NLRP3)-mediated IL-33 activation via a reactive oxygen species (ROS) -NRF2- Heme oxygenase-1(HO-1)-NF-кB axis. Free radical biology & medicine 22 36990300
2011 GRIM-19 disrupts E6/E6AP complex to rescue p53 and induce apoptosis in cervical cancers. PloS one 22 21765936
2016 Mitochondrial GRIM-19 as a potential therapeutic target for STAT3-dependent carcinogenesis of gastric cancer. Oncotarget 21 27167343
2018 Expression of GRIM-19 in unexplained recurrent spontaneous abortion and possible pathogenesis. Molecular human reproduction 20 29741731
2008 GRIM-19 in Health and Disease. Advances in anatomic pathology 20 18156812
2016 GRIM-19 inhibition induced autophagy through activation of ERK and HIF-1α not STAT3 in Hela cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 19 26810068
2007 [Correlations of GRIM-19 and its target gene product STAT3 to malignancy of human colorectal carcinoma]. Ai zheng = Aizheng = Chinese journal of cancer 19 17626740
2016 Curcumin synergistically increases effects of β-interferon and retinoic acid on breast cancer cells in vitro and in vivo by up-regulation of GRIM-19 through STAT3-dependent and STAT3-independent pathways. Journal of drug targeting 18 27677346
2013 Small interfering RNA survivin and GRIM-19 co-expression salmonella plasmid inhibited the growth of laryngeal cancer cells in vitro and in vivo. International journal of clinical and experimental pathology 18 24133585
2023 Metformin suppresses cardiac fibroblast proliferation under high-glucose conditions via regulating the mitochondrial complex I protein Grim-19 involved in the Sirt1/Stat3 signaling pathway. Free radical biology & medicine 17 37353174
2016 Grim19 Attenuates DSS Induced Colitis in an Animal Model. PloS one 17 27258062
2016 GRIM19 ameliorates acute graft-versus-host disease (GVHD) by modulating Th17 and Treg cell balance through down-regulation of STAT3 and NF-AT activation. Journal of translational medicine 17 27391226
2009 GRIM-19 inhibits v-Src-induced cell motility by interfering with cytoskeletal restructuring. Oncogene 17 19151760
2014 Overexpression of GRIM-19, a mitochondrial respiratory chain complex I protein, suppresses hepatocellular carcinoma growth. International journal of clinical and experimental pathology 16 25550785
2012 Expression and clinical significance of GRIM-19 in lung cancer. Medical oncology (Northwood, London, England) 16 22573109
2020 Novel NDUFA13 Mutations Associated with OXPHOS Deficiency and Leigh Syndrome: A Second Family Report. Genes 15 32722639
2016 Expression of NDUFA13 in asthenozoospermia and possible pathogenesis. Reproductive biomedicine online 15 27789183
2016 High Glucose Induces Down-Regulated GRIM-19 Expression to Activate STAT3 Signaling and Promote Cell Proliferation in Cell Culture. PloS one 14 27101310
2012 Plasmid-based Survivin shRNA and GRIM-19 carried by attenuated Salmonella suppresses tumor cell growth. Asian journal of andrology 14 22580637
2010 Identification of alternatively spliced GRIM-19 mRNA in kidney cancer tissues. Journal of human genetics 14 20505682
2007 The IFN-beta and retinoic acid-induced cell death regulator GRIM-19 is upregulated during focal cerebral ischemia. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 14 17523870
2012 Absence of the BRAF and the GRIM-19 mutations in oncocytic (Hürthle cell) solid cell nests of the thyroid. American journal of clinical pathology 13 22431538
2022 GRIM-19 is a target of mycobacterial Zn2+ metalloprotease 1 and indispensable for NLRP3 inflammasome activation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 12 34907600
2021 GRIM19 Impedes Obesity by Regulating Inflammatory White Fat Browning and Promoting Th17/Treg Balance. Cells 12 33467683
2010 Identification of a structural motif in the tumor-suppressive protein GRIM-19 required for its antitumor activity. The American journal of pathology 12 20595633
2007 Differential effects of all-trans retinoic acid on the growth of human keratinocytes and mouth carcinoma epidermoid cultures. Involvement of GRIM-19 and complex I of the respiratory chain. International journal of immunopathology and pharmacology 12 18179744
2021 GRIM-19 inhibits proliferation and induces apoptosis in a p53-dependent manner in colorectal cancer cells through the SIRT7/PCAF/MDM2 axis. Experimental cell research 11 34461110
2022 Grim-19 deficiency promotes decidual macrophage autophagy in recurrent spontaneous abortion. Frontiers in endocrinology 10 36387896
2018 Overexpression of GRIM-19 accelerates radiation-induced osteosarcoma cells apoptosis by p53 stabilization. Life sciences 10 30005830
2018 Repression of GRIM19 expression potentiates cisplatin chemoresistance in advanced bladder cancer cells via disrupting ubiquitination-mediated Bcl-xL degradation. Cancer chemotherapy and pharmacology 10 30032449
2017 GRIM-19, a gene associated with retinoid-interferon-induced mortality, affects endometrial receptivity and embryo implantation. Reproduction, fertility, and development 10 27346638
2014 Plasmid-based Stat3-specific siRNA and GRIM-19 inhibit the growth of thyroid cancer cells in vitro and in vivo. Oncology reports 10 24899100
2010 The cell death regulator GRIM-19 is involved in HIV-1 induced T-cell apoptosis. Apoptosis : an international journal on programmed cell death 10 20640890
2024 GRIM-19-mediated induction of mitochondrial STAT3 alleviates systemic sclerosis by inhibiting fibrosis and Th2/Th17 cells. Experimental & molecular medicine 9 39643607
2019 GRIM-19 over-expression represses the proliferation and invasion of orthotopically implanted hepatocarcinoma tumors associated with downregulation of Stat3 signaling. Bioscience trends 9 31527330
2024 Mitochondrial GRIM19 Loss Induces Liver Fibrosis through NLRP3/IL33 Activation via Reactive Oxygen Species/NF-кB Signaling. Journal of clinical and translational hepatology 8 38974954
2024 SGK3 deficiency in macrophages suppresses angiotensin II-induced cardiac remodeling via regulating Ndufa13-mediated mitochondrial oxidative stress. Cellular and molecular life sciences : CMLS 8 39158709
2017 GRIM-19 represses the proliferation and invasion of cutaneous squamous cell carcinoma cells associated with downregulation of STAT3 signaling. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 8 28926927
2015 Enhanced antitumor effect of cisplatin in human oral squamous cell carcinoma cells by tumor suppressor GRIM‑19. Molecular medicine reports 8 26458285
2015 The GRIM-19 plays a vital role in shrimps' responses to Vibrio alginolyticus. Fish & shellfish immunology 8 26702559
2014 Synergistic effects of co-expression plasmid‑based ADAM10-specific siRNA and GRIM-19 on hepatocellular carcinoma in vitro and in vivo. Oncology reports 8 25242535
2014 GRIM‑19‑mediated Stat3 activation is a determinant for resveratrol‑induced proliferation and cytotoxicity in cervical tumor‑derived cell lines. Molecular medicine reports 8 25351437
2010 The knockdown of Ha-GRIM-19 by RNA interference induced programmed cell death. Amino acids 8 21184119
2021 Structural exploration with AlphaFold2-generated STAT3α structure reveals selective elements in STAT3α-GRIM-19 interactions involved in negative regulation. Scientific reports 7 34848745
2020 Interaction of M2 macrophages and endometrial cells induces downregulation of GRIM-19 in endometria of adenomyosis. Reproductive biomedicine online 7 32896475
2020 GRIM-19 Ameliorates Multiple Sclerosis in a Mouse Model of Experimental Autoimmune Encephalomyelitis with Reciprocal Regulation of IFNγ/Th1 and IL-17A/Th17 Cells. Immune network 7 33163248
2015 Upregulation of GRIM-19 inhibits the growth and invasion of human breast cancer cells. Molecular medicine reports 7 25955394
2015 Expression of GW112 and GRIM-19 in colorectal cancer tissues. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 7 26011333
2014 Upregulation of GRIM-19 suppresses the growth of oral squamous cell carcinoma in vitro and in vivo. Oncology reports 7 25174621
2013 GRIM-19 mutations fail to inhibit v-Src-induced oncogenesis. Oncogene 7 23851499
2012 Expression and functional characterization of a gene associated with retinoid-interferon-induced mortality 19 (GRIM-19) from orange-spotted grouper (Epinephelus coioides). Fish & shellfish immunology 7 23178692
2009 [Expression and clinical significance of GRIM-19 in non-small cell lung cancer]. Ai zheng = Aizheng = Chinese journal of cancer 7 19622307
2023 GRIM-19 in asthenozoospermia regulates GC-2 spd cell proliferation, apoptosis and migration. Scientific reports 6 36813832
2023 LncRNA SATB2-AS1 overexpression represses the development of hepatocellular carcinoma through regulating the miR-3678-3p/GRIM-19 axis. Cancer cell international 6 37118800
2017 miR-6743-5p, as a direct upstream regulator of GRIM-19, enhances proliferation and suppresses apoptosis in glioma cells. Bioscience reports 6 29074558
2018 Retinoid interferon-induced mortality19 (GRIM19) inhibits proliferation and invasion in rheumatoid arthritis fibroblast-like synoviocytes. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 5 29306209
2018 Taurolidine promotes cell apoptosis by enhancing GRIM‑19 expression in liver cancer. Oncology reports 5 30272302
2010 GRIM-19 Expression and Function in Human Gliomas. Journal of Korean Neurosurgical Society 5 20717508

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