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Vol. 14, Issue 4, 1583-1596, April 2003
and
*Institute of Medical Technology and Tampere University
Hospital, Lenkkeilijänkatu 6, 33014 University of Tampere,
Tampere, Finland; 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 colocalization 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 colocalize with
Twinkle in intramitochondrial foci defined as nucleoids by the specific
incorporation of bromodeoxyuridine. Furthermore, mtDNA polymerase POLG
and various other as yet unidentified proteins copurify 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 redistribute in the mitochondrial network and
suggest that nucleoids are the mitochondrial units of inheritance.
Nucleoids did not colocalize with dynamin-related protein 1, Drp1, a
protein of the mitochondrial fission machinery.
Department of Biological
Chemistry, David Geffen School of Medicine, UCLA, Los Angeles,
California 90095; and Electron Microscopy Unit,
Institute of Biotechnology, 00014 University of Helsinki, Helsinki,
Finland
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