The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA
Open accessAbstract
Mammalian mtDNA is packaged in DNA-protein complexes denoted mitochondrial nucleoids. The organization of the nucleoid is a very fundamental question in mitochondrial biology and will determine tissue segregation and transmission of mtDNA. We have used a combination of stimulated emission depletion microscopy, enabling a resolution well below the diffraction barrier, and molecular biology to study nucleoids in a panel of mammalian tissue culture cells. We report that the nucleoids labeled with antibodies against DNA, mitochondrial transcription factor A (TFAM), or incorporated BrdU, have a defined, uniform mean size of ∼100 nm in mammals. Interestingly, the nucleoid frequently contains only a single copy of mtDNA (average ∼1.4 mtDNA molecules per nucleoid). Furthermore, we show by molecular modeling and volume calculations that TFAM is a main constituent of the nucleoid, besides mtDNA. These fundamental insights into the organization of mtDNA have broad implications for understanding mitochondrial dysfunction in disease and aging.
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Cites
Coot : model-building tools for molecular graphics
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Mitochondrial transcription factor A regulates mtDNA copy number in mammals
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“In vivo data from mouse models has demonstrated that disruption of the Tfam gene leads to loss of mtDNA and embryonic lethality (17), whereas increase of TFAM protein levels leads to increase of mtDNA copy number (13).”
BackgroundResultAn ancestral mitochondrial DNA resembling a eubacterial genome in miniature
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Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA
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“Recombinant human TFAM was purified as described previously (37) and analyzed by mass spectrometry (see below).”
MethodSelf-citation
Cited by
Mitochondrial form and function
Friedman, J. R., & Nunnari, J. (2014) · Nature · doi:10.1038/nature12985 · Cited by 1,803
Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs
Phinney, D. G., Di Giuseppe, M., Njah, J., Sala, E., Shiva, S., St Croix, C. M., Stolz, D. B., Watkins, S. C., Di, Y. P., Leikauf, G. D., et al. (2015) · Nature Communications · doi:10.1038/ncomms9472 · Cited by 1,007
Fluorescence nanoscopy in cell biology
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Self-citationStructure and function of mitochondrial membrane protein complexes
Kühlbrandt, W. (2015) · BMC Biology · doi:10.1186/s12915-015-0201-x · Cited by 699
ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells
Lewis, S. C., Uchiyama, L. F., & Nunnari, J. (2016) · Science · doi:10.1126/science.aaf5549 · Cited by 673
Metadata
- Authors
- Kukat, C., Wurm, C. A., Spåhr, H., Falkenberg, M., Larsson, N.-G., & Jakobs, S.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2011-08
- Volume
- 108
- Issue
- 33
- Pages
- 13534-13539
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2057695252
- Cited by
- 563
- References
- 5
- FWCI
- 11.99
- Type
- journal article
- Language
- en
- Open access
- green
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- Kukat, C., Wurm, C. A., Spåhr, H., Falkenberg, M., Larsson, N.-G., & Jakobs, S. (2011). Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1109263108
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