Abstract
Mutations in mitochondrial DNA (mtDNA) generate multi-system disorders due to failure of ATP production. A cybrid containing a 1.9-kb mtDNA deletion from a patient with Kearns Sayre Syndrome is respiration-defective and grows glycolytically. When treated with a ribonucleoprotein (RNP) complex of polycistronic RNA 1 (pcRNA1) containing mtDNA-encoded genes and a multi-subunit carrier complex R8, full-length pcRNA1 was transported to mitochondria. Translation of the pcRNA1-encoded mRNAs was observed in mitochondria from RNP-treated cells. Respiration of the cybrid was rescued to approximately 90% of normal within hours, switching the cells to aerobic growth. These findings have implications for the development of effective mitochondrial gene therapy.
© 2011 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / biosynthesis
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Base Sequence
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Cell Line
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Cell Respiration
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Chromosome Mapping
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DNA, Mitochondrial / genetics
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DNA, Mitochondrial / metabolism*
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Electron Transport Complex IV / metabolism
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Gene Expression Profiling
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Gene Transfer Techniques*
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Genetic Therapy
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Humans
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Kearns-Sayre Syndrome / genetics*
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Kearns-Sayre Syndrome / therapy
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Membrane Potential, Mitochondrial
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Mitochondria / genetics
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Mitochondria / metabolism
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Mitochondria / physiology*
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Oxidative Phosphorylation
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Oxygen / metabolism
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RNA Transport
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Messenger / pharmacology
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RNA, Transfer / metabolism
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Ribonucleoproteins / metabolism
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Ribonucleoproteins / pharmacology*
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Sequence Deletion
Substances
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DNA, Mitochondrial
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RNA, Messenger
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Ribonucleoproteins
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Adenosine Triphosphate
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RNA, Transfer
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Electron Transport Complex IV
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Oxygen