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A more recent version of this article appeared on April 1, 2003
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Submitted on July 15, 2002
Revised on October 17, 2002
Accepted on November 27, 2002
1 Institute of Medical Technology and Tampere University Hospital, Lenkkeilijänkatu 6, 33014 University of Tampere, Tampere, Finland
2 Department of Biological Chemistry, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA
3 Electron Microscopy Unit, Institute of Biotechnology, P.O. Box 56, 00014 University of Helsinki, Helsinki, Finland
* Corresponding author. E-mail address: hans.spelbrink{at}uta.fi.
The organization of multiple mitochondrial DNA (mtDNA) molecules in discrete protein-DNA complexes called nucleoids is well studied in Saccharomyces cerevisiae. Similar structures have recently been observed in human cells by the co-localization of a Twinkle-GFP fusion protein with mtDNA. However, nucleoids in mammalian cells are poorly characterized and are often thought of as relatively simple structures, despite the yeast paradigm. In this article we have used immunocytochemistry and biochemical isolation procedures to characterize the composition of human mitochondrial nucleoids. The results show that both the mitochondrial transcription factor TFAM and mitochondrial single-stranded DNA-binding protein co-localize with Twinkle in intra-mitochondrial foci defined as nucleoids by the specific incorporation of bromodeoxyuridine. Furthermore, mtDNA polymerase POLG and various other as yet unidentified proteins co-purify with mtDNA nucleoids using a biochemical isolation procedure, as does TFAM. The results demonstrated that mtDNA in mammalian cells is organized in discrete protein-rich structures within the mitochondrial network. In vivo time-lapse imaging of nucleoids show they are dynamic structures able to divide and re-distribute in the mitochondrial network, and suggest that nucleoids are the mitochondrial units of inheritance. Nucleoids did not co-localize with dynamin-related protein 1, Drp1, a protein of the mitochondrial fission machinery.
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