Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 33, Pages 13534-13539Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1109263108
Keywords
mitochondria; nanoscopy
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Funding
- Deutsche Forschungsgemeinschaft [SFB 829]
- Deutsche Forschungsgemeinschaft Research Center for Molecular Physiology of the Brain
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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 similar to 100 nm in mammals. Interestingly, the nucleoid frequently contains only a single copy of mtDNA (average similar to 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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