Affinage

NDUFA13

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

Length
144 aa
Mass
16.7 kDa
Annotated
2026-04-29
100 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NDUFA13 (GRIM-19) is an essential accessory subunit of mitochondrial respiratory chain Complex I that links oxidative phosphorylation to cell death signaling, STAT3 regulation, and innate immunity. It is required for Complex I assembly, stability, electron transfer activity, and maintenance of mitochondrial membrane potential, with homozygous knockout causing embryonic lethality and germline mutations causing early-onset neurological disease (PMID:15367666, PMID:25901006, PMID:18287540). NDUFA13 directly binds STAT3 via a phospho-S727-dependent interaction and an N-terminal structural motif, functioning both as an inhibitor of STAT3 nuclear transcriptional activity and as a chaperone that recruits STAT3 to the mitochondrial inner membrane through Tom20; loss of this interaction—including by tumor-derived somatic mutations—derepresses STAT3 signaling and promotes oncogenesis (PMID:12628925, PMID:12867595, PMID:23271731, PMID:24145455, PMID:23386605). NDUFA13 mediates electron leak-driven cytosolic H₂O₂ production that activates NLRP3 inflammasome-dependent caspase-1/IL-1β responses during infection and cardioprotective STAT3 dimerization during ischemia-reperfusion injury (PMID:29078279, PMID:34907600, PMID:22665480).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2000 High

    Establishing that GRIM-19 is a cell-death effector answered the question of what genes mediate IFN-β/retinoic acid-induced tumor cell killing, positioning it as a novel death regulator before its mitochondrial identity was known.

    Evidence Antisense knockout genetic screen with gain- and loss-of-function validation in tumor cell lines

    PMID:10924506

    Open questions at the time
    • Molecular mechanism of death induction unknown
    • No mitochondrial connection yet established
    • Endogenous regulation of GRIM-19 expression uncharacterized
  2. 2001 High

    Identifying GRIM-19 as a bona fide Complex I subunit resolved the paradox of a death gene being a housekeeping respiratory chain component, unifying its proapoptotic and metabolic functions.

    Evidence Mass spectrometric peptide sequencing of purified bovine Complex I subcomplex Iλ

    PMID:11522775

    Open questions at the time
    • Whether GRIM-19 is required for Complex I assembly versus only structural
    • How a Complex I subunit participates in cell death signaling
  3. 2003 High

    Discovery of the direct, selective GRIM-19–STAT3 interaction and its dependence on STAT3-S727 phosphorylation established GRIM-19 as a specific STAT3 inhibitor acting at the transactivation domain level, independent of STAT3 DNA binding or tyrosine phosphorylation.

    Evidence Yeast two-hybrid, reciprocal co-immunoprecipitation, point mutant analysis (S727A), reporter assays in two independent laboratories

    PMID:12628925 PMID:12867595

    Open questions at the time
    • Structural basis of the GRIM-19–STAT3 interface unresolved
    • Whether the interaction occurs in the nucleus, cytoplasm, or mitochondria
    • Physiological consequence of STAT3 inhibition in non-tumor contexts unknown
  4. 2004 High

    Knockout mice proved GRIM-19 is essential for Complex I assembly and embryonic viability, demonstrating it is not merely a structural passenger but a required assembly factor whose loss destroys Complex I and affects other respiratory complexes.

    Evidence Homozygous knockout mice lethal at E9.5; native immunoprecipitation and electron transfer activity assays in embryonic cells

    PMID:15367666

    Open questions at the time
    • Step at which GRIM-19 acts in CI assembly pathway undefined
    • Whether heterozygous loss has phenotypic consequences in specific tissues
  5. 2005 Medium

    Identifying the GRIM-19–NOD2 interaction linked mitochondrial Complex I biology to innate immune pattern recognition, showing GRIM-19 is required for NF-κB activation downstream of muramyl dipeptide sensing.

    Evidence Yeast two-hybrid, endogenous co-immunoprecipitation in intestinal epithelial cells, siRNA knockdown with bacterial invasion and NF-κB reporter assays

    PMID:15753091

    Open questions at the time
    • Whether the NOD2 interaction is direct or bridged by STAT3
    • Not replicated by an independent group
    • Mechanism linking GRIM-19 to NF-κB activation unclear
  6. 2007 Medium

    Multiple viral proteins (KSHV vIRF1, HPV E6, HHV-6B U95) were shown to target GRIM-19, establishing it as a convergent viral immune-evasion target whose neutralization disrupts both mitochondrial function and IFN-mediated cell death.

    Evidence Yeast two-hybrid, co-immunoprecipitation, mitochondrial membrane potential and cell death assays across separate viral systems

    PMID:12163600 PMID:17297443 PMID:17928352

    Open questions at the time
    • Structural details of viral protein–GRIM-19 interfaces unknown
    • In vivo relevance during natural viral infection not demonstrated
  7. 2008 High

    Domain mapping resolved which GRIM-19 regions are required for mitochondrial localization, membrane potential maintenance, and Complex I incorporation, showing that these are genetically separable functions.

    Evidence Systematic deletion/truncation mutant analysis with mitochondrial membrane potential, Complex I assembly, and apoptosis readouts

    PMID:18287540

    Open questions at the time
    • No high-resolution structure of GRIM-19 within Complex I
    • How the dominant-negative mutant disrupts ΔΨm while assembled into CI is mechanistically unclear
  8. 2010 Medium

    Identification of an N-terminal motif required for STAT3 binding and tumor suppression explained how tumor-derived point mutations selectively abolish the STAT3-inhibitory arm of GRIM-19 without necessarily destroying Complex I function.

    Evidence N-terminal deletion/point mutant analysis with co-immunoprecipitation, reporter, and growth assays

    PMID:20595633 PMID:23386605

    Open questions at the time
    • Whether tumor mutations also affect Complex I assembly in patient tissues not tested
    • No crystal structure of the N-terminal motif
  9. 2012 High

    Demonstrating that GRIM-19 chaperones STAT3 into the mitochondrial inner membrane via Tom20 established a non-transcriptional mitochondrial role for STAT3 dependent on GRIM-19, with S727 phosphorylation gating import efficiency.

    Evidence In vitro mitochondrial import assay, sub-mitochondrial fractionation, co-immunoprecipitation, S727A mutagenesis

    PMID:23271731

    Open questions at the time
    • Whether GRIM-19 directly contacts Tom20 or acts through an adaptor unknown
    • Stoichiometry of the GRIM-19–STAT3–Tom20 import complex not defined
  10. 2012 High

    Linking RIPK1-dependent STAT3-S727 phosphorylation to GRIM-19-mediated mitochondrial STAT3 translocation and ROS during necroptosis placed GRIM-19 at the nexus of programmed necrosis and mitochondrial signaling.

    Evidence siRNA knockdown, necrostatin-1 inhibition, phospho-specific immunoblotting, mitochondrial fractionation, ROS measurement

    PMID:22393233

    Open questions at the time
    • Whether GRIM-19 is a RIPK3 substrate or only a passive chaperone unknown
    • Downstream mechanism by which mitochondrial STAT3 increases ROS not resolved
  11. 2013 High

    Conditional skin-specific heterozygous GRIM-19 deletion was sufficient to promote carcinogenesis with elevated STAT3 activity and disrupted ETC assembly, providing the first in vivo genetic proof that GRIM-19 haploinsufficiency is tumor-promoting.

    Evidence Conditional knockout mice with chemical carcinogenesis, Complex I assembly, STAT3 activity, and gene expression analysis

    PMID:24145455

    Open questions at the time
    • Whether tumor promotion is driven primarily by STAT3 derepression or ETC dysfunction or both
    • Applicability to other tissue types unknown
  12. 2015 High

    Identification of the first germline NDUFA13 mutation in patients with neurological disease and severely reduced Complex I established NDUFA13 as a Mendelian mitochondrial disease gene.

    Evidence Patient mutation identification, BN-PAGE for CI holoenzyme/supercomplexes, enzymatic activity assay, siRNA phenocopy in control cells

    PMID:25901006

    Open questions at the time
    • Only one family reported; allelic spectrum unknown
    • Whether STAT3 dysregulation contributes to the neurological phenotype not tested
  13. 2017 High

    Cardiac-specific heterozygous NDUFA13 deletion revealed that partial Complex I deficiency causes site-specific electron leak generating cytosolic (not mitochondrial matrix) H₂O₂, which drives protective STAT3 dimerization during ischemia-reperfusion, providing the first compartment-resolved ROS signaling model for this subunit.

    Evidence Tamoxifen-inducible cardiac conditional knockout, ischemia-reperfusion model, compartment-specific H₂O₂ sensors, STAT3 dimerization assay

    PMID:29078279

    Open questions at the time
    • Precise electron leak site within CI not mapped at atomic resolution
    • Whether chronic cytosolic H₂O₂ has deleterious long-term cardiac effects unknown
  14. 2022 High

    CRISPR knockout in macrophages proved GRIM-19 is required for NLRP3 inflammasome activation via mitochondrial ROS, connecting Complex I integrity to innate immune IL-1β production during mycobacterial infection.

    Evidence CRISPR/Cas9 knockout macrophage line, mitochondrial ROS, caspase-1 activation, NLRP3 stimulation with ATP and nigericin

    PMID:34907600

    Open questions at the time
    • Whether GRIM-19 acts upstream of NLRP3 solely through ROS or also through direct protein interaction
    • Relevance to non-mycobacterial NLRP3 triggers in vivo not fully tested
  15. 2024 Medium

    Demonstration that GRIM-19 recruits STAT3 to mitochondria via Tom20 to induce mitophagy and alleviate fibrosis extended GRIM-19's mitochondrial chaperone role to a disease-relevant mitophagy pathway.

    Evidence GRIM-19 overexpression in bleomycin-induced systemic sclerosis mouse model, mitochondrial fractionation, mitophagy assay, Tom20 interaction assay

    PMID:39643607

    Open questions at the time
    • Whether mitophagy induction requires STAT3 or is a parallel GRIM-19 function
    • Tom20 interaction not yet mapped at the residue level
    • Single-lab finding awaiting independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structural model of GRIM-19 within the intact human Complex I that explains both its electron-leak site and its STAT3-binding interface remains unavailable, and the mechanism by which partial GRIM-19 loss shifts ROS production to the cytosolic compartment is unresolved.
  • No atomic-resolution structure of GRIM-19 with STAT3 or within human CI
  • Mechanism of selective cytosolic vs. matrix ROS generation not molecularly defined
  • Relative contributions of STAT3 derepression vs. ETC dysfunction to tumorigenesis not genetically separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6 GO:0005198 structural molecule activity 4 GO:0044183 protein folding chaperone 2
Localization
GO:0005739 mitochondrion 6 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3
Partners
E6APHTRA2NOD2RIPK1STAT3TOMM20
Complex memberships
Mitochondrial Complex I (NADH:ubiquinone oxidoreductase)

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 GRIM-19/NDUFA13 is a bona fide subunit of bovine mitochondrial NADH:ubiquinone oxidoreductase (Complex I), identified by mass-spectrometric peptide sequencing of subcomplex Iλ (hydrophilic arm), with the N-terminus shown to be acetylated. Denaturing gel electrophoresis of Complex I subcomplex, tryptic digestion, mass spectrometry, cDNA cloning, intact protein mass measurement The Journal of biological chemistry High 11522775
2000 GRIM-19 is induced by the IFN-β/retinoic acid combination and is required for IFN/RA-induced tumor cell death; antisense inactivation of GRIM-19 confers resistance to cell death and overexpression enhances it. Antisense knockout genetic screen, overexpression and antisense expression assays in tumor cell lines The Journal of biological chemistry High 10924506
2003 GRIM-19 physically interacts with STAT3 (but not STAT1 or STAT5a), co-localizes with STAT3 at perinuclear mitochondrial aggregates, inhibits STAT3 nuclear translocation stimulated by EGF, and represses STAT3 transcriptional activity and target gene expression. Yeast two-hybrid screen, co-immunoprecipitation, co-localization with mitochondrial markers, domain mapping, reporter assays, growth suppression assays The EMBO journal High 12628925 12867595
2003 GRIM-19 binds specifically to STAT3 (not STAT1) via the STAT3 transactivation domain; residue S727 of STAT3 is required for GRIM-19 binding. GRIM-19 inhibits STAT3-driven transcription without blocking STAT3 tyrosine phosphorylation or DNA binding. Yeast two-hybrid screen, co-immunoprecipitation, point mutant analysis, reporter gene assays Proceedings of the National Academy of Sciences of the United States of America High 12867595
2004 GRIM-19 is essential for Complex I assembly and electron transfer activity; homozygous knockout in mice causes embryonic lethality at E9.5 with abnormal mitochondrial structure and distribution, and loss of GRIM-19 destroys Complex I assembly and influences other respiratory chain complexes. Gene targeting/knockout mice, native Complex I immunoprecipitation, electron transfer activity assay, mitochondrial morphology analysis Molecular and cellular biology High 15367666
2008 Functional domain mapping shows that the mitochondrial localization sequence of GRIM-19 is at its N-terminus; deletion of residues 70–80, 90–100, or the C-terminal region (70–144) abolishes mitochondrial transmembrane potential (ΔΨm); deletion of the last 10 C-terminal residues prevents assembly into Complex I; a dominant-negative mutant assembled into Complex I but failed to maintain ΔΨm and sensitized cells to apoptosis. Deletion/truncation/point mutant analysis, mitochondrial membrane potential assay, Complex I assembly assay, apoptosis assay Molecular biology of the cell High 18287540
2012 GRIM-19 acts as a chaperone to recruit STAT3 into the inner mitochondrial membrane and enhances STAT3 integration into Complex I; the STAT3 S727A mutation reduces import and Complex I assembly even in the presence of GRIM-19. In vitro mitochondrial import assay, sub-mitochondrial fractionation, co-immunoprecipitation, site-directed mutagenesis The Journal of biological chemistry High 23271731
2012 During TNF-induced necroptosis, RIPK1-dependent phosphorylation of STAT3 on S727 induces its interaction with GRIM-19, leading to mitochondrial translocation of STAT3, increased mitochondrial ROS production, and cell death. siRNA knockdown of RIPK1, necrostatin-1 inhibition, phospho-specific immunoblotting, co-immunoprecipitation, mitochondrial fractionation, ROS measurement Journal of cell science High 22393233
2002 KSHV vIRF1 directly interacts with GRIM-19 via its N-terminal region, co-localizes with GRIM-19, deregulates GRIM-19-induced apoptosis, and inhibits IFN/RA-induced cell death; HPV16 E6 also binds GRIM-19. Yeast two-hybrid, co-immunoprecipitation (in vivo and in vitro), confocal co-localization, cell death assay Journal of virology Medium 12163600
2005 GRIM-19 interacts with NOD2 in intestinal epithelial cells and is required for NF-κB activation following NOD2-mediated recognition of muramyl dipeptide and for control of pathogen invasion. Yeast two-hybrid, endogenous co-immunoprecipitation in HT29 cells, siRNA knockdown, bacterial invasion assay, NF-κB reporter assay The Journal of biological chemistry Medium 15753091
2007 GRIM-19 physically interacts with the serine protease HtrA2, augments HtrA2-driven destruction of XIAP in an IFN/RA-dependent manner, and promotes cell death; vIRF1 disrupts this interaction to confer resistance to IFN/RA-induced death. Yeast two-hybrid, co-immunoprecipitation, cell death assay, XIAP degradation assay Oncogene Medium 17297443
2007 GRIM-19 suppresses v-Src-induced cellular transformation and metastasis by inhibiting STAT3-dependent gene expression and by suppressing tyrosyl phosphorylation of focal adhesion kinase, paxillin, E-cadherin, and γ-catenin independently of STAT3. Overexpression and shRNA knockdown, in vitro transformation assay, in vivo metastasis assay, phospho-Western blotting The American journal of pathology Medium 17823279
2009 GRIM-19 inhibits v-Src-induced cell motility and podosome formation through its N-terminal domain, independently of STAT3; tumor-associated GRIM-19 mutations disrupt this activity and fail to upregulate the lipid raft-associated Src inhibitor Pag1. N-terminal deletion and point mutant analysis, podosome formation assay, cell motility assay, in vivo metastasis assay Oncogene Medium 19151760
2011 GRIM-19 disrupts the HPV18 E6/E6AP complex by interacting with both E6 and E6AP via its N-terminus, promotes E6AP ubiquitination and degradation, and thereby rescues p53 from degradation and promotes apoptosis in cervical cancer cells. Co-immunoprecipitation, GST pull-down, competition pull-down assay, in vivo and in vitro ubiquitination assay, xenograft tumor model PloS one Medium 21765936
2012 Heterozygous GRIM-19 knockout macrophages have compromised Complex I activity and elevated ROS, leading to decreased intracellular bacterial killing and reduced proinflammatory cytokine production; bacterial infection normally upregulates GRIM-19 and Complex I activity in wild-type macrophages. Heterozygous knockout mice, Complex I activity assay, ROS measurement, intracellular bacterial killing assay, cytokine ELISA, in vivo infection model The Journal of biological chemistry High 22665480
2013 Tumor-derived somatic mutations in GRIM-19 (L71P, L91P, A95T) cause loss of STAT3 binding, loss of suppression of STAT3 transcriptional activity, and failure to suppress cellular transformation and metastasis in vitro and in vivo. Somatic mutation screening of primary tumors, co-immunoprecipitation, transformation assay, in vivo tumor growth and metastasis assay The Journal of biological chemistry Medium 23386605
2013 Monoallelic skin-specific deletion of GRIM-19 is sufficient to promote chemical carcinogenesis and invasive squamous cell carcinoma, associated with high STAT3 activity, upregulated STAT3-responsive genes, mitochondrial electron transport dysfunction, and failure to assemble ETC complexes. Conditional knockout mice, chemical carcinogenesis protocol, Complex I assembly assay, STAT3 activity assay, gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 24145455
2013 GRIM-19 opposes the Warburg effect in glioblastoma by destabilizing HIF-1α: GRIM-19 loss promotes STAT3-dependent HIF-1α synthesis and prevents pVHL-mediated HIF-1α ubiquitination/proteasomal degradation. Overexpression/knockdown in glioblastoma cell lines, HIF-1α protein stability assays, pVHL interaction assay, STAT3 inhibitor Carcinogenesis Medium 23580587
2015 The first germline pathogenic mutation in NDUFA13/GRIM-19 is identified in patients with early onset hypotonia, dyskinesia, and optic neuropathy; patient cells show drastically reduced Complex I enzymatic activity, reduced CI-driven respiration, and loss of NDUFA13 protein, CI holoenzyme, and supercomplexes; NDUFA13 silencing in control cells reproduces CI instability. Patient mutation identification, biochemical analysis of muscle biopsies and fibroblasts, BN-PAGE for Complex I holoenzyme and supercomplexes, Western blot, siRNA knockdown Human molecular genetics High 25901006
2017 Cardiac-specific heterozygous NDUFA13 knockout mice show basal-state cytosolic H2O2 elevation (not mitochondrial), which drives STAT3 dimerization and antiapoptotic signaling, reducing infarct size during ischemia-reperfusion injury; NDUFA13 is positioned near low-electrochemical-potential subunits of Complex I and mediates electron leak. Tamoxifen-inducible cardiac-specific conditional knockout mice, I/R injury model, H2O2 compartment-specific measurement, oxygen consumption rate assay, STAT3 dimerization assay Proceedings of the National Academy of Sciences of the United States of America High 29078279
2021 GRIM-19 suppresses colorectal cancer cell proliferation and induces apoptosis through posttranslational stabilization of p53: GRIM-19 activates SIRT7, which triggers PCAF-mediated MDM2 ubiquitination, reducing MDM2-dependent p53 degradation. Overexpression/KD in CRC cells, xenograft model, co-immunoprecipitation, ubiquitination assay, siRNA epistasis Experimental cell research Medium 34461110
2010 An N-terminal structural motif of GRIM-19 bearing similarity to RNA viral proteins is required for STAT3 interaction and antitumor activity; disruption of specific amino acids in this motif or a clinically observed mutation weakens STAT3 binding and ablates growth suppression. N-terminal deletion and point mutant analysis, co-immunoprecipitation, reporter gene assay, cell growth assay The American journal of pathology Medium 20595633
2007 HHV-6B U95 protein interacts with GRIM-19 (confirmed by Co-IP and confocal co-localization), and U95 expression induces loss of mitochondrial membrane potential and mitochondrial ultrastructural damage; siRNA knockdown of U95 abrogates the loss of mitochondrial membrane potential. Yeast two-hybrid, co-immunoprecipitation, confocal immunolocalization, mitochondrial membrane potential assay, RNA interference Journal of virology Medium 17928352
2016 NDUFA13/GRIM-19 deficiency in sperm midpiece (shown by immunofluorescence) reduces mitochondrial membrane potential, increases ROS, and increases apoptosis; siRNA knockdown in GC2-spd spermatocyte cells reproduces these effects, linking NDUFA13 to sperm motility. Immunofluorescence localization, mitochondrial membrane potential assay, ROS measurement, apoptosis assay, siRNA knockdown Reproductive biomedicine online Medium 27789183
2022 GRIM-19 is a novel binding partner of Mycobacterium tuberculosis Zmp1 metalloprotease; GRIM-19 knockout (CRISPR) macrophages show loss of mitochondrial ROS generation and NLRP3-dependent caspase-1 activation, demonstrating that GRIM-19 is required for NLRP3 inflammasome activation and IL-1β production during mycobacterial infection. CRISPR/Cas9 knockout macrophage line, protein interaction assay, mitochondrial ROS assay, caspase-1 activation assay, NLRP3 stimuli (ATP, nigericin), mitochondrial membrane potential assay FASEB journal High 34907600
2024 GRIM-19 overexpression increases mitochondrial STAT3 levels, induces mitophagy, and alleviates fibrosis in a bleomycin-induced systemic sclerosis model; GRIM-19 recruits STAT3 to mitochondria via the mitochondrial importer Tom20. GRIM-19 overexpression in SSc mouse model, mitochondrial fractionation, mitophagy assay, fibrosis histology, Tom20 interaction assay 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 183 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 158 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 50 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
2010 Overexpression of GRIM-19 in cancer cells suppresses STAT3-mediated signal transduction and cancer growth. Molecular cancer therapeutics 32 20682646
2018 Inhibition of miR-423-5p suppressed prostate cancer through targeting GRIM-19. Gene 31 30415005
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
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 27 33174032
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 14 32722639
2016 High Glucose Induces Down-Regulated GRIM-19 Expression to Activate STAT3 Signaling and Promote Cell Proliferation in Cell Culture. PloS one 14 27101310
2016 Expression of NDUFA13 in asthenozoospermia and possible pathogenesis. Reproductive biomedicine online 14 27789183
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
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
2022 Grim-19 deficiency promotes decidual macrophage autophagy in recurrent spontaneous abortion. Frontiers in endocrinology 9 36387896
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
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 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
2024 Mitochondrial GRIM19 Loss Induces Liver Fibrosis through NLRP3/IL33 Activation via Reactive Oxygen Species/NF-кB Signaling. Journal of clinical and translational hepatology 7 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 7 39158709
2024 GRIM-19-mediated induction of mitochondrial STAT3 alleviates systemic sclerosis by inhibiting fibrosis and Th2/Th17 cells. Experimental & molecular medicine 7 39643607
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
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
2015 Enhanced antitumor effect of cisplatin in human oral squamous cell carcinoma cells by tumor suppressor GRIM‑19. Molecular medicine reports 7 26458285
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 LncRNA SATB2-AS1 overexpression represses the development of hepatocellular carcinoma through regulating the miR-3678-3p/GRIM-19 axis. Cancer cell international 6 37118800
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 6 33163248
2017 miR-6743-5p, as a direct upstream regulator of GRIM-19, enhances proliferation and suppresses apoptosis in glioma cells. Bioscience reports 6 29074558
2021 [Pathogenic role of NDUFA13 inactivation in spontaneous hepatitis in mice and the mechanism]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 5 33509753
2019 Upregulation of GRIM-19 augments the sensitivity of prostate cancer cells to docetaxel by targeting Rad23b. Clinical and experimental pharmacology & physiology 5 31531888
2018 Retinoid interferon-induced mortality19 (GRIM19) inhibits proliferation and invasion in rheumatoid arthritis fibroblast-like synoviocytes. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 5 29306209
2011 [Expressions of survivin and GRIM-19 in prostate cancer]. Zhonghua nan ke xue = National journal of andrology 5 21351527