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Vol. 11, Issue 4, 1471-1485, April 2000
Departments of *Genetics and Development and
Mitochondria from patients with Kearns-Sayre syndrome harboring
large-scale rearrangements of human mitochondrial DNA (mtDNA; both
partial deletions and a partial duplication) were introduced into human
cells lacking endogenous mtDNA. Cytoplasmic hybrids containing
100% wild-type mtDNA, 100% mtDNA with partial duplications, and 100%
mtDNA with partial deletions were isolated and characterized. The cell
lines with 100% deleted mtDNAs exhibited a complete impairment of
respiratory chain function and oxidative phosphorylation. In contrast,
there were no detectable respiratory chain or protein synthesis defects
in the cell lines with 100% duplicated mtDNAs. Unexpectedly, the mass
of mtDNA was identical in all cell lines, despite the fact that
different lines contained mtDNAs of vastly different sizes and with
different numbers of replication origins, suggesting that mtDNA copy
number may be regulated by tightly controlled mitochondrial dNTP pools.
In addition, quantitation of mtDNA-encoded RNAs and polypeptides in
these lines provided evidence that mtDNA gene copy number affects gene
expression, which, in turn, is regulated at both the
post-transcriptional and translational levels.
Neurology, Columbia University, New York, New York
10032; §Universitäts-Kinderklinik, Abteilung
Pädiatrie/Neuropädiatrie, D-37075 Göttingen, Germany;
Unidad de Investigación Médica en
Genética Humana, Hospital de Pediatria, Centro Médico
Nacional, Mexico City, Mexico D.F. 03020; and ¶Department
of Biochemistry and Molecular Pharmacology, Thomas Jefferson
University, Philadelphia, Pennsylvania 19107
Corresponding author. E-mail address:
yt62{at}columbia.edu.
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