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J Biol Chem, Vol. 273, Issue 6, 3447-3451, February 6, 1998
From the Departments of § Internal Medicine,
¶ Molecular Biology/Oncology, and Mitochondrial biogenesis and mitochondrial DNA
(mtDNA) replication are regulated during development and in response to
physiological stresses, but the regulatory events that control the
abundance of mtDNA in cells of higher eukaryotes have not been defined
at a molecular level. In this study, we observed that expression of the
catalytic subunit of DNA polymerase
Differential Expression of Mitochondrial DNA Replication Factors
in Mammalian Tissues
,,, Pathology,
University of Texas Southwestern Medical Center, Dallas, Texas
75235
(POLCAT)
mRNA varies little among different tissues and is not increased by
continuous neural activation of skeletal muscle, a potent stimulus to
mitochondrial biogenesis. Increased copy number for the POL locus in
a human cell line bearing a partial duplication of chromosome 15 increased the abundance of POLCAT mRNA without
up-regulation of mtDNA. In contrast, expression of mitochondrial
single-stranded DNA-binding (mtSSB) mRNA is regulated coordinately
with variations in the abundance of mtDNA among tissues of mammalian
organisms and is up-regulated in association with the enhanced
mitochondrial biogenesis that characterizes early postnatal development
of the heart and the adaptive response of skeletal myofibers to motor
nerve stimulation. In addition, we noted that expression of mtSSB is
concentrated within perinuclear mitochondria that constitute active
sites of mtDNA replication. We conclude that constitutive expression of the gene encoding the catalytic subunit of mitochondrial DNA polymerase is sufficient to support physiological variations in mtDNA replication among specialized cell types, whereas expression of the mtSSB gene is
controlled by molecular mechanisms acting to regulate mtDNA replication
or stability in mammalian cells.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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