Protein Components of Mitochondrial DNA Nucleoids in Higher Eukaryotes

Bogenhagen, Daniel F.; Wang, Yousong; Shen, Ellen L.; Kobayashi, Ryûji

doi:10.1074/mcp.m300035-mcp200

Cited by 136 publications

(102 citation statements)

References 57 publications

(51 reference statements)

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“…We have used similar gradients containing metrizamide to characterize Xenopus mtDNA nucleoids previously (32). Nucleoids were identified in the buoyant density gradient by their content of DNA, determined by SYBR Green I fluorescence, and the presence of the abundant DNA-binding protein TFAM.…”

Section: Resultsmentioning

confidence: 99%

“…Oligonucleotide primers were synthesized with sequences having 3Ј-termini 4 or 5 nucleotides away from known 2Ј-O-ribose modification sites in domain 5 (5Ј-GGTTGGGTTCTGCTCCGAGG) or domain 6 (5Ј-GAT-CACGTAGGACTTTAATCG) of human 16 S rRNA. Primers were labeled at 5Ј-termini using [␥- 32 P]ATP and polynucleotide kinase and were purified by electrophoresis on urea-14% polyacrylamide gels. Labeled primers were annealed to 500 ng of crude mtRNA or T7 transcript in first strand buffer for Superscript 3 reverse transcriptase (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

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Mitochondrial Ribosomal RNA (rRNA) Methyltransferase Family Members Are Positioned to Modify Nascent rRNA in Foci near the Mitochondrial DNA Nucleoid

Lee

Okot-Kotber²,

LaComb

et al. 2013

Journal of Biological Chemistry

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Background: Mitochondrial rRNAs contain site-specific modifications, including methylated residues, but few of the enzymes responsible for these modifications have been found. Results: RNMTL1, MRM1, and MRM2 are methyltransferase family members found associated with the mtDNA nucleoid and with the large ribosomal subunit. Conclusion:The association of putative RNA-modifying enzymes with nucleoids and ribosomes supports the model that assembly of mitochondrial ribosomes begins while rRNA transcription continues. Significance: This work advances understanding of the assembly of mitochondrial ribosomes necessary for biosynthesis of the respiratory chain.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Mitochondrial Ribosomal RNA (rRNA) Methyltransferase Family Members Are Positioned to Modify Nascent rRNA in Foci near the Mitochondrial DNA Nucleoid

Lee

Okot-Kotber²,

LaComb

et al. 2013

Journal of Biological Chemistry

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“…The mtDNA is not organised in nucleosomal bodies but instead associated with the mitochondrial inner membrane and several proteins including mitochondrial transcription factor A (mtTFA) and mitochondrial single-stranded DNA binding protein (mtSSB) (Bogenhagen et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Genetic aspects of mitochondrial genome evolution

Bernt

Braband

Schierwater

et al. 2013

Molecular Phylogenetics and Evolution

219

148

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“…Nucleoids are DNA-protein structures that are important in mtDNA maintenance and stability (2)(3)(4). For this purpose, we used an antibody raised against double-stranded DNA that recognizes the mtDNAenriched nucleoids (2).…”

Section: Activation Of Mitochondrially Targeted Restriction Endonucleasementioning

confidence: 99%

“…mtDNA, the only extrachromosomal DNA in the cell, encodes for components of the oxidative phosphorylation system (OXPHOS), and it is located within the mitochondrial matrix in discrete protein-DNA complexes called nucleoids (1)(2)(3)(4). Most pathogenic mtDNA mutations exist in a heteroplasmic state, and several studies have shown that a high percentage of mutated mtDNA is necessary to trigger a metabolic defect in specific tissues and organs (5,6).…”

mentioning

confidence: 99%

Rapid directional shift of mitochondrial DNA heteroplasmy in animal tissues by a mitochondrially targeted restriction endonuclease

Bayona‐Bafaluy

Blits

Battersby

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

144

122

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Frequently, mtDNA with pathogenic mutations coexist with wildtype genomes (mtDNA heteroplasmy). Mitochondrial dysfunction and disease ensue only when the proportion of mutated mtDNAs is high, thus a reduction in this proportion should provide an effective therapy for these disorders. We developed a system to decrease specific mtDNA haplotypes by expressing a mitochondrially targeted restriction endonuclease, ApaLI, in cells of heteroplasmic mice. These mice have two mtDNA haplotypes, of which only one contains an ApaLI site. After transfection of cultured hepatocytes with mitochondrially targeted ApaLI, we found a rapid, directional, and complete shift in mtDNA heteroplasmy (2-6 h). We tested the efficacy of this approach in vivo, by using recombinant viral vectors expressing the mitochondrially targeted ApaLI. We observed a significant shift in mtDNA heteroplasmy in muscle and brain transduced with recombinant viruses. This strategy could prevent disease onset or reverse clinical symptoms in patients harboring certain heteroplasmic pathogenic mutations in mtDNA.gene therapy ͉ mitochondria

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Protein Components of Mitochondrial DNA Nucleoids in Higher Eukaryotes

Cited by 136 publications

References 57 publications

Mitochondrial Ribosomal RNA (rRNA) Methyltransferase Family Members Are Positioned to Modify Nascent rRNA in Foci near the Mitochondrial DNA Nucleoid

Mitochondrial Ribosomal RNA (rRNA) Methyltransferase Family Members Are Positioned to Modify Nascent rRNA in Foci near the Mitochondrial DNA Nucleoid

Genetic aspects of mitochondrial genome evolution

Rapid directional shift of mitochondrial DNA heteroplasmy in animal tissues by a mitochondrially targeted restriction endonuclease

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