Home LiteratureArticle Details
PMID: 22453275 Published · ppublish English Journal Article Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis.

Nucleic acids research ·Vol. 40 ·No. 13 ·2012-07-00 ·Pages 6109-21

He J, Cooper HM, Reyes A, Di Re M, Sembongi H, Litwin TR, Gao J, Neuman KC, Fearnley IM, Spinazzola A, Walker JE, Holt IJ

Abstract

Mitochondrial ribosomes and translation factors co-purify with mitochondrial nucleoids of human cells, based on affinity protein purification of tagged mitochondrial DNA binding proteins. Among the most frequently identified proteins were ATAD3 and prohibitin, which have been identified previously as nucleoid components, using a variety of methods. Both proteins are demonstrated to be required for mitochondrial protein synthesis in human cultured cells, and the major binding partner of ATAD3 is the mitochondrial ribosome. Altered ATAD3 expression also perturbs mtDNA maintenance and replication. These findings suggest an intimate association between nucleoids and the machinery of protein synthesis in mitochondria. ATAD3 and prohibitin are tightly associated with the mitochondrial membranes and so we propose that they support nucleic acid complexes at the inner membrane of the mitochondrion.

MeSH Terms
ATPases Associated with Diverse Cellular Activities Adenosine Triphosphatases/metabolism Cell Cycle Proteins/physiology Cell Line, Tumor DNA, Mitochondrial/metabolism HEK293 Cells Humans Membrane Proteins/metabolism Mitochondria/genetics Mitochondrial Proteins/biosynthesis,metabolism,physiology Nuclear Proteins/physiology Nucleoproteins/physiology Prohibitins Protein Biosynthesis RNA/analysis,isolation & purification RNA, Messenger/analysis RNA, Mitochondrial Repressor Proteins/physiology Ribosomes/metabolism
Chemicals
ATAD3A protein, human ATAD3B protein, human Cell Cycle Proteins DNA, Mitochondrial GADD45GIP1 protein, human Membrane Proteins Mitochondrial Proteins Nuclear Proteins Nucleoproteins Prohibitins RNA, Messenger RNA, Mitochondrial Repressor Proteins RNA Adenosine Triphosphatases ATPases Associated with Diverse Cellular Activities
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
He J
MRC-Mitochondrial Biology Unit, Wellcome Trust-MRC Building, Hills Road Cambridge, CB2 0XY, UK.
Cooper H M
Reyes A
Di Re M
Sembongi H
Litwin T R
Gao J
Neuman K C
Fearnley I M
Spinazzola A
Walker J E
Holt I J
References (44)
44 references, click to expand
  1. In vivo methylation of mtDNA reveals the dynamics of protein-mtDNA interactions.
    Nucleic Acids Res. 2009 Nov;37(20):6701-15 PMID: 19740762
  2. C. elegans ATAD-3 is essential for mitochondrial activity and development.
    PLoS One. 2009 Oct 30;4(10):e7644 PMID: 19888333
  3. Functional requirement of a site-specific ribose methylation in ribosomal RNA.
    Science. 1993 Dec 17;262(5141):1886-9 PMID: 8266080
  4. The GTP binding protein Obg homolog ObgE is involved in ribosome maturation.
    Genes Cells. 2005 May;10(5):393-408 PMID: 15836769
  5. Complex I deficiency is associated with 3243G:C mitochondrial DNA in osteosarcoma cell cybrids.
    Hum Mol Genet. 1996 Jan;5(1):123-29 PMID: 8789449
  6. Prohibitin function within mitochondria: essential roles for cell proliferation and cristae morphogenesis.
    Biochim Biophys Acta. 2009 Jan;1793(1):27-32 PMID: 18558096
  7. Leucine-rich pentatricopeptide-repeat containing protein regulates mitochondrial transcription.
    Biochemistry. 2010 Sep 7;49(35):7467-73 PMID: 20677761
  8. The accessory subunit of mitochondrial DNA polymerase gamma determines the DNA content of mitochondrial nucleoids in human cultured cells.
    Nucleic Acids Res. 2009 Sep;37(17):5701-13 PMID: 19625489
  9. TEFM (c17orf42) is necessary for transcription of human mtDNA.
    Nucleic Acids Res. 2011 May;39(10):4284-99 PMID: 21278163
  10. Properties of the C-terminal tail of human mitochondrial inner membrane protein Oxa1L and its interactions with mammalian mitochondrial ribosomes.
    J Biol Chem. 2010 Sep 3;285(36):28353-62 PMID: 20601428
  11. A mitochondrial protein compendium elucidates complex I disease biology.
    Cell. 2008 Jul 11;134(1):112-23 PMID: 18614015
  12. Mitochondrial and nuclear genomic responses to loss of LRPPRC expression.
    J Biol Chem. 2010 Apr 30;285(18):13742-7 PMID: 20220140
  13. Pentatricopeptide repeat domain protein 3 associates with the mitochondrial small ribosomal subunit and regulates translation.
    FEBS Lett. 2009 Jun 18;583(12):1853-8 PMID: 19427859
  14. CR6-interacting factor 1 interacts with Gadd45 family proteins and modulates the cell cycle.
    J Biol Chem. 2003 Jul 25;278(30):28079-88 PMID: 12716909
  15. Mitochondrial disease in flies.
    Biochim Biophys Acta. 2004 Dec 6;1659(2-3):190-6 PMID: 15576051
  16. ERAL1 is associated with mitochondrial ribosome and elimination of ERAL1 leads to mitochondrial dysfunction and growth retardation.
    Nucleic Acids Res. 2010 Sep;38(16):5554-68 PMID: 20430825
  17. Prohibitins control cell proliferation and apoptosis by regulating OPA1-dependent cristae morphogenesis in mitochondria.
    Genes Dev. 2008 Feb 15;22(4):476-88 PMID: 18281461
  18. Tid1 isoforms are mitochondrial DnaJ-like chaperones with unique carboxyl termini that determine cytosolic fate.
    J Biol Chem. 2006 May 12;281(19):13150-13158 PMID: 16531398
  19. Probability-based protein identification by searching sequence databases using mass spectrometry data.
    Electrophoresis. 1999 Dec;20(18):3551-67 PMID: 10612281
  20. Twinkle helicase is essential for mtDNA maintenance and regulates mtDNA copy number.
    Hum Mol Genet. 2004 Dec 15;13(24):3219-27 PMID: 15509589
  21. Protein components of mitochondrial DNA nucleoids in higher eukaryotes.
    Mol Cell Proteomics. 2003 Nov;2(11):1205-16 PMID: 14514796
  22. Identifying specific protein interaction partners using quantitative mass spectrometry and bead proteomes.
    J Cell Biol. 2008 Oct 20;183(2):223-39 PMID: 18936248
  23. Human ERAL1 is a mitochondrial RNA chaperone involved in the assembly of the 28S small mitochondrial ribosomal subunit.
    Biochem J. 2010 Sep 15;430(3):551-8 PMID: 20604745
  24. The human mitochondrial ribosome recycling factor is essential for cell viability.
    Nucleic Acids Res. 2008 Oct;36(18):5787-99 PMID: 18782833
  25. Structure of the mammalian mitochondrial ribosome reveals an expanded functional role for its component proteins.
    Cell. 2003 Oct 3;115(1):97-108 PMID: 14532006
  26. Mammalian mitochondrial nucleoids: organizing an independently minded genome.
    Mitochondrion. 2007 Sep;7(5):311-21 PMID: 17698423
  27. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification.
    Nat Biotechnol. 2008 Dec;26(12):1367-72 PMID: 19029910
  28. Actin and myosin contribute to mammalian mitochondrial DNA maintenance.
    Nucleic Acids Res. 2011 Jul;39(12):5098-108 PMID: 21398640
  29. LRPPRC and SLIRP interact in a ribonucleoprotein complex that regulates posttranscriptional gene expression in mitochondria.
    Mol Biol Cell. 2010 Apr 15;21(8):1315-23 PMID: 20200222
  30. Human prohibitin 1 maintains the organization and stability of the mitochondrial nucleoids.
    Exp Cell Res. 2008 Mar 10;314(5):988-96 PMID: 18258228
  31. Interaction of mitochondrial elongation factor Tu with aminoacyl-tRNA and elongation factor Ts.
    J Biol Chem. 2000 Jul 7;275(27):20308-14 PMID: 10801827
  32. The AAA+ ATPase ATAD3A controls mitochondrial dynamics at the interface of the inner and outer membranes.
    Mol Cell Biol. 2010 Apr;30(8):1984-96 PMID: 20154147
  33. Human mitochondrial DNA nucleoids are linked to protein folding machinery and metabolic enzymes at the mitochondrial inner membrane.
    J Biol Chem. 2006 Sep 1;281(35):25791-802 PMID: 16825194
  34. Morphogenesis of the endoplasmic reticulum: beyond active membrane expansion.
    Traffic. 2006 Jun;7(6):639-46 PMID: 16683914
  35. The layered structure of human mitochondrial DNA nucleoids.
    J Biol Chem. 2008 Feb 8;283(6):3665-3675 PMID: 18063578
  36. Mitochondrial p32 protein is a critical regulator of tumor metabolism via maintenance of oxidative phosphorylation.
    Mol Cell Biol. 2010 Mar;30(6):1303-18 PMID: 20100866
  37. Similarity of human mitochondrial transcription factor 1 to high mobility group proteins.
    Science. 1991 May 17;252(5008):965-9 PMID: 2035027
  38. Fast kinase domain-containing protein 3 is a mitochondrial protein essential for cellular respiration.
    Biochem Biophys Res Commun. 2010 Oct 22;401(3):440-6 PMID: 20869947
  39. Human small G proteins, ObgH1, and ObgH2, participate in the maintenance of mitochondria and nucleolar architectures.
    Genes Cells. 2006 Nov;11(11):1295-304 PMID: 17054726
  40. Ribosome assembly factors prevent premature translation initiation by 40S assembly intermediates.
    Science. 2011 Sep 9;333(6048):1449-53 PMID: 21835981
  41. The organization and inheritance of the mitochondrial genome.
    Nat Rev Genet. 2005 Nov;6(11):815-25 PMID: 16304597
  42. Branched-chain amino acid metabolon: interaction of glutamate dehydrogenase with the mitochondrial branched-chain aminotransferase (BCATm).
    J Biol Chem. 2010 Jan 1;285(1):265-76 PMID: 19858196
  43. Replication of vertebrate mitochondrial DNA entails transient ribonucleotide incorporation throughout the lagging strand.
    EMBO J. 2006 Nov 15;25(22):5358-71 PMID: 17066082
  44. The AAA+ protein ATAD3 has displacement loop binding properties and is involved in mitochondrial nucleoid organization.
    J Cell Biol. 2007 Jan 15;176(2):141-6 PMID: 17210950
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gks266
Published
2012-07-00
Epub
2012-00-26
Pages
6109-21
Language
English
Region
England
NLM ID
0411011
PMCID
PMC3401451
Subset
IM
Grants
Medical Research Council · MC_U105663148 · United Kingdom
Medical Research Council · MC_U105663140 · United Kingdom
Biotechnology and Biological Sciences Research Council · BB/F012802/1 · United Kingdom
Intramural NIH HHS · United States
Medical Research Council · MC_U105697134 · United Kingdom
External Links
PubMed source DOI: 10.1093/nar/gks266 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