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 of the United States of America - Tập 108 Số 33 - Trang 13534-13539 - 2011
Christian Kukat1, Christian A. Wurm2,3, Henrik Spåhr1, Maria Falkenberg4,5, Nils‐Göran Larsson1, Stefan Jakobs2,3
1Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, D-50931 Cologne, Germany
2Department of NanoBiophotonics, Mitochondrial Structure and Dynamics Group, Max Planck Institute for Biophysical Chemistry, and
3Department of Neurology, University of Göttingen, D-37077 Göttingen, Germany; and
4Department of Medical Biochemistry and Cell Biology, University of Gothenburg; SE-40530 Gothenburg, Sweden
5Max Planck Society

Tóm tắt

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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Proceedings of the National Academy of Sciences of the United States of America

Tập 108 Số 33

13534-13539

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