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Published online June 23, 2008
doi:10.1083/jcb.200712101
The Journal of Cell Biology, Vol. 181, No. 7, 1117-1128
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Gilkerson et al.
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Mitochondrial nucleoids maintain genetic autonomy but allow for functional complementation

Robert W. Gilkerson1, Eric A. Schon1,2, Evelyn Hernandez1, and Mercy M. Davidson1

1 Department of Neurology and 2 Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032

Correspondence to Eric A. Schon: eas3{at}columbia.edu

Mitochondrial DNA (mtDNA) is packaged into DNA-protein assemblies called nucleoids, but the mode of mtDNA propagation via the nucleoid remains controversial. Two mechanisms have been proposed: nucleoids may consistently maintain their mtDNA content faithfully, or nucleoids may exchange mtDNAs dynamically. To test these models directly, two cell lines were fused, each homoplasmic for a partially deleted mtDNA in which the deletions were nonoverlapping and each deficient in mitochondrial protein synthesis, thus allowing the first unequivocal visualization of two mtDNAs at the nucleoid level. The two mtDNAs transcomplemented to restore mitochondrial protein synthesis but were consistently maintained in discrete nucleoids that did not intermix stably. These results indicate that mitochondrial nucleoids tightly regulate their genetic content rather than freely exchanging mtDNAs. This genetic autonomy provides a molecular mechanism to explain patterns of mitochondrial genetic inheritance, in addition to facilitating therapeutic methods to eliminate deleterious mtDNA mutations.

Abbreviations used in this paper: mtDNA, mitochondrial DNA; PEG, polyethylene glycol; WT, wild type.

© 2008 Gilkerson et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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