- Authors: Kukat C.,Wurm C.A., Spahr H.,Falkenberg M., Larsson N., Jakobs S.
- Title: Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA
- Journal: Proc. Natl. Acad. Sci. USA
- Volume: 108
- Volume: 13534-13539
- DOI: 10.1073/pnas.1109263108
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.