| Functional complementation of mitochondrial DNAs: mobilizing mitochondrial genetics against dysfunction. | |
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MedLine Citation:
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PMID: 19616602 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Human mitochondrial DNA (mtDNA) is a 16.6-kb circular genome that is typically found in approximately 1000 copies per cell. Frequently, one or more forms of mtDNA (i.e. wildtype (WT) and one or more mutant variants) will co-exist within an individual cell, a situation termed heteroplasmy; however, it has been unclear how different mitochondria and mtDNA populations interact functionally in a heteroplasmic cell system. Using sequence-specific microscopic methods to examine mtDNA at suborganellar resolution, we examined the submitochondrial organization of mtDNA heteroplasmy in nucleoids, the DNA-protein complexes that organize and package mtDNA. Our recent results reveal that, while heterologous mtDNAs are generally maintained stably in separate nucleoid populations, the two mtDNAs transcomplement each other to restore WT-like levels of mitochondrial function and morphology. These findings reveal that the diffusion of mtDNA-derived transcripts through the mitochondrial matrix allows for transcomplementation, despite the apparent genetic autonomy of nucleoids. The fundamental ability of mtDNAs to complement each other within the matrix of the mitochondrial network provides a mechanistic basis for therapeutic strategies designed to restore mitochondrial function in heteroplasmic cells by increasing WT mtDNA content, particularly in light of the emerging connection between the processes of mitochondrial fission/fusion and mtDNA nucleoid organization. |
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Authors:
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Eric A Schon; Robert W Gilkerson |
Publication Detail:
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Type: Journal Article; Review Date: 2009-07-17 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1800 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-02-22 Completed Date: 2010-05-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 245-9 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2009 Elsevier B.V. All rights reserved. |
Affiliation:
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Department of Neurology, College of Physicians and Surgeons, Columbia University, Russ Berrie Pavilion 307, 1150 St. Nicholas Ave., New York, NY 10032, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism DNA, Circular / genetics DNA, Mitochondrial / genetics* Genetic Complementation Test* Genetic Variation Genome Humans Image Processing, Computer-Assisted MELAS Syndrome / genetics Mitochondria / genetics*, metabolism, pathology Mitochondrial Membranes / metabolism, pathology Oxygen Consumption Transcription Factors / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/DNA, Circular; 0/DNA, Mitochondrial; 0/Transcription Factors; 56-65-5/Adenosine Triphosphate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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