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DNA Delivery to Mitochondria: Sequence Specificity and Energy Enhancement
- Source :
- Pharmaceutical Research. 28:2871-2882
- Publication Year :
- 2011
- Publisher :
- Springer Science and Business Media LLC, 2011.
-
Abstract
- 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.
- Subjects :
- Mitochondrial DNA
Mitochondrial disease
Genetic Vectors
Molecular Sequence Data
Drug Evaluation, Preclinical
Pharmaceutical Science
Biology
Mitochondrion
Zea mays
chemistry.chemical_compound
Adenosine Triphosphate
Drug Delivery Systems
Organelle
medicine
Humans
Pharmacology (medical)
Amino Acid Sequence
Phosphorylation
Peptide sequence
Pharmacology
Organic Chemistry
Gene Transfer Techniques
DNA
Transfection
Phosphoproteins
medicine.disease
Molecular biology
In vitro
Mitochondria
Cell biology
Protein Transport
chemistry
Molecular Medicine
Carmovirus
Biotechnology
Subjects
Details
- ISSN :
- 1573904X and 07248741
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Pharmaceutical Research
- Accession number :
- edsair.doi.dedup.....5238d122dd772601e26da14350baa6a7