Super-resolution Microscopy Reveals That Mammalian Mitochondrial Nucleoids Have a Uniform Size and Frequently Contain a Single Copy of MtDNA

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2011 Aug 3

PMID 21808029

Citations 259

Authors

Christian Kukat

Christian A Wurm

Henrik Spahr

Maria Falkenberg

Nils-Goran Larsson

Stefan Jakobs

Affiliations

Soon will be listed here.

Abstract

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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