DNA Delivery to Mitochondria: Sequence Specificity and Energy Enhancement
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Mitochondria are competent for DNA uptake in vitro, a mechanism which may support delivery of therapeutic DNA to complement organelle DNA mutations. We document here key aspects of the DNA import process, so as to further lay the ground for mitochondrial transfection in intact cells.
We developed DNA import assays with isolated mitochondria from different organisms, using DNA substrates of various sequences and sizes. Further import experiments investigated the possible role of ATP and protein phosphorylation in the uptake process. The fate of adenine nucleotides and the formation of phosphorylated proteins were analyzed.
We demonstrate that the efficiency of mitochondrial uptake depends on the sequence of the DNA to be translocated. The process becomes sequence-selective for large DNA substrates. Assays run with a natural mitochondrial plasmid identified sequence elements which promote organellar uptake. ATP enhances DNA import and allows tight integration of the exogenous DNA into mitochondrial nucleoids. ATP hydrolysis has to occur during the DNA uptake process and might trigger phosphorylation of co-factors.
Our data contribute critical information to optimize DNA delivery into mitochondria and open the prospect of targeting whole mitochondrial genomes or complex constructs into mammalian organelles in vitro and in vivo.
- DNA Delivery to Mitochondria: Sequence Specificity and Energy Enhancement
Volume 28, Issue 11 , pp 2871-2882
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- Springer US
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- DNA import
- mitochondrial disease
- mitochondrial plasmid
- organelle transfection
- protein phosphorylation
- Industry Sectors
- Author Affiliations
- 1. Institut de Biologie Moléculaire des Plantes, CNRS and Université de Strasbourg, 12 rue du Général Zimmer, 67084, Strasbourg, France
- 2. Mitochondrial Research Group, Institute for Aging & Health Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK
- 3. Plant Genome Research Unit, National Institute of Agrobiological Sciences, 2-1-2 Kan-non-dai, Tsukuba, 305–8602, Japan
- 4. Siberian Institute of Plant Physiology and Biochemistry, Russian Academy of Sciences, Ul. Lermontova 132, Irkutsk, 664033, Russia