Home LiteratureArticle Details
PMID: 15367666 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

GRIM-19, a cell death regulatory protein, is essential for assembly and function of mitochondrial complex I.

Molecular and cellular biology ·Vol. 24 ·No. 19 ·2004-10-00 ·Pages 8447-56

Huang G, Lu H, Hao A, Ng DC, Ponniah S, Guo K, Lufei C, Zeng Q, Cao X

Abstract

Mitochondria play essential roles in cellular energy production via the oxidative phosphorylation system (OXPHOS) consisting of five multiprotein complexes and also in the initiation of apoptosis. NADH:ubiquinone oxidoreductase (complex I) is the largest complex that catalyzes the first step of electron transfer in the OXPHOS system. GRIM-19 was originally identified as a nuclear protein with apoptotic nature in interferon (IFN)- and all-trans-retinoic acid (RA)-induced tumor cells. To reveal its biological role, we generated mice deficient in GRIM-19 by gene targeting. Homologous deletion of GRIM-19 causes embryonic lethality at embryonic day 9.5. GRIM-19(-/-) blastocysts show retarded growth in vitro and, strikingly, display abnormal mitochondrial structure, morphology, and cellular distribution. We reexamined the cellular localization of GRIM-19 in various cell types and found its primary localization in the mitochondria. Furthermore, GRIM-19 is detected in the native form of mitochondrial complex I. Finally, we show that elimination of GRIM-19 destroys the assembly and electron transfer activity of complex I and also influences the other complexes in the mitochondrial respiratory chain. Our result demonstrates that GRIM-19, a gene product with a specific role in IFN-RA-induced cell death, is a functional component of mitochondrial complex I and is essential for early embryonic development.

MeSH Terms
Animals Apoptosis/genetics,physiology Blastocyst/pathology Cell Division/genetics,physiology Electron Transport Complex I/metabolism Mice Mice, Knockout Microscopy, Confocal Mitochondria/metabolism,pathology NADH, NADPH Oxidoreductases/deficiency,genetics,metabolism Sequence Deletion
Chemicals
NADH, NADPH Oxidoreductases Grim19 protein, mouse Electron Transport Complex I
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Huang Guochang
Signal Transduction Laboratory, Institute of Molecular and Cell Biology, Proteos Building, Room 6-19B, 61 Biopolis Dr., Singapore 138673, Republic of Singapore.
Lu Hao
Hao Aijun
Ng Dominic C H
Ponniah Sathivel
Guo Ke
Lufei Chengchen
Zeng Qi
Cao Xinmin
References (37)
37 references, click to expand
  1. Disruption of the COP9 signalosome Csn2 subunit in mice causes deficient cell proliferation, accumulation of p53 and cyclin E, and early embryonic death.
    Mol Cell Biol. 2003 Oct;23(19):6790-7 PMID: 12972599
  2. The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification.
    J Biol Chem. 2003 Apr 18;278(16):13619-22 PMID: 12611891
  3. GW112, a novel antiapoptotic protein that promotes tumor growth.
    Cancer Res. 2004 Apr 1;64(7):2474-81 PMID: 15059901
  4. The mitochondrial electron transport and oxidative phosphorylation system.
    Annu Rev Biochem. 1985;54:1015-69 PMID: 2862839
  5. The respiratory-chain NADH dehydrogenase (complex I) of mitochondria.
    Eur J Biochem. 1991 May 8;197(3):563-76 PMID: 2029890
  6. Blue native electrophoresis for isolation of membrane protein complexes in enzymatically active form.
    Anal Biochem. 1991 Dec;199(2):223-31 PMID: 1812789
  7. The NADH:ubiquinone oxidoreductase (complex I) of respiratory chains.
    Q Rev Biophys. 1992 Aug;25(3):253-324 PMID: 1470679
  8. Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway.
    Cell. 1994 Apr 8;77(1):63-71 PMID: 7512451
  9. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins.
    Science. 1994 Jun 3;264(5164):1415-21 PMID: 8197455
  10. Analysis of molecular masses and oligomeric states of protein complexes by blue native electrophoresis and isolation of membrane protein complexes by two-dimensional native electrophoresis.
    Anal Biochem. 1994 Mar;217(2):220-30 PMID: 8203750
  11. Retinoic acid and interferon in human cancer: mechanistic and clinical studies.
    Semin Hematol. 1994 Oct;31(4 Suppl 5):31-7 PMID: 7831583
  12. Vitamin A, differentiation and cancer.
    Curr Opin Cell Biol. 1994 Dec;6(6):825-31 PMID: 7880529
  13. Quantification of muscle mitochondrial oxidative phosphorylation enzymes via histochemical staining of blue native polyacrylamide gels.
    Electrophoresis. 1997 Oct;18(11):2059-64 PMID: 9420170
  14. Procaryotic complex I (NDH-1), an overview.
    Biochim Biophys Acta. 1998 May 6;1364(2):125-33 PMID: 9593856
  15. How cells respond to interferons.
    Annu Rev Biochem. 1998;67:227-64 PMID: 9759489
  16. Thioredoxin reductase mediates cell death effects of the combination of beta interferon and retinoic acid.
    Mol Cell Biol. 1998 Nov;18(11):6493-504 PMID: 9774665
  17. NADH:ubiquinone oxidoreductase from bovine heart mitochondria: sequence of a novel 17.2-kDa subunit.
    FEBS Lett. 1998 Nov 6;438(3):301-5 PMID: 9827566
  18. Synergistic antitumor effects of a combination of interferons and retinoic acid on human tumor cells in vitro and in vivo.
    Clin Cancer Res. 1997 Jun;3(6):931-7 PMID: 9815768
  19. Mitochondrial diseases in man and mouse.
    Science. 1999 Mar 5;283(5407):1482-8 PMID: 10066162
  20. Oxidative phosphorylation at the fin de siècle.
    Science. 1999 Mar 5;283(5407):1488-93 PMID: 10066163
  21. Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions.
    Biochem J. 1999 Sep 1;342 ( Pt 2):249-68 PMID: 10455009
  22. The nuclear encoded subunits of complex I from bovine heart mitochondria.
    Biochim Biophys Acta. 2003 Jul 10;1604(3):135-50 PMID: 12837546
  23. The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3.
    Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9342-7 PMID: 12867595
  24. Supercomplexes in the respiratory chains of yeast and mammalian mitochondria.
    EMBO J. 2000 Apr 17;19(8):1777-83 PMID: 10775262
  25. Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics.
    Genome Res. 2000 May;10(5):703-13 PMID: 10810093
  26. Cytochrome c deficiency causes embryonic lethality and attenuates stress-induced apoptosis.
    Cell. 2000 May 12;101(4):389-99 PMID: 10830166
  27. Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-beta and retinoic acid combination, using a genetic approach.
    J Biol Chem. 2000 Oct 27;275(43):33416-26 PMID: 10924506
  28. The Stat family in cytokine signaling.
    Curr Opin Cell Biol. 2001 Apr;13(2):211-7 PMID: 11248555
  29. Structures and proton-pumping strategies of mitochondrial respiratory enzymes.
    Annu Rev Biophys Biomol Struct. 2001;30:23-65 PMID: 11340051
  30. Mitochondrial diseases: beyond the magic circle.
    Am J Med Genet. 2001 Spring;106(1):1-3 PMID: 11579419
  31. Respiratory chain complex I deficiency.
    Am J Med Genet. 2001 Spring;106(1):37-45 PMID: 11579423
  32. GRIM-19, a cell death regulatory gene product, is a subunit of bovine mitochondrial NADH:ubiquinone oxidoreductase (complex I).
    J Biol Chem. 2001 Oct 19;276(42):38345-8 PMID: 11522775
  33. Isolation and characterization of intact mitochondria from neonatal rat brain.
    Brain Res Brain Res Protoc. 2001 Dec;8(3):176-83 PMID: 11733193
  34. Mitochondria: releasing power for life and unleashing the machineries of death.
    Cell. 2003 Feb 21;112(4):481-90 PMID: 12600312
  35. GRIM-19, a death-regulatory gene product, suppresses Stat3 activity via functional interaction.
    EMBO J. 2003 Mar 17;22(6):1325-35 PMID: 12628925
  36. Analysis of the subunit composition of complex I from bovine heart mitochondria.
    Mol Cell Proteomics. 2003 Feb;2(2):117-26 PMID: 12644575
  37. Identification and characterization of a common set of complex I assembly intermediates in mitochondria from patients with complex I deficiency.
    J Biol Chem. 2003 Oct 31;278(44):43081-8 PMID: 12941961
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.24.19.8447-8456.2004
Published
2004-10-00
Pages
8447-56
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC516758
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.24.19.8447-8456.2004 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2