Mitochondria-specificity

BOLA-LIPID-BASED MITOCHONDRIA-SPECIFIC DELIVERY SYSTEMS... 

Based on the intrinsic mitochondriotropism of dequalinium and its unique self-assembly behavior, we have developed a strategy for direct mitochondrial transfection (47-49), which involves the transport of a DNA-mitochondrial leader sequence (MLS) peptide conjugate to mitochondria using DQAsomes, the liberation of this conjugate from the cationic vector upon contact with the mitochondrial outer membrane followed by DNA uptake via the mitochondrial protein import machinery. We have demonstrated that DQAsomes fulfill all essential prerequisites for a mitochondria-specific DNA delivery system they bind and condense pDNA (24), protect it from... 

It should be emphasized at this point that the use of physicochemical methods is so far the only way to demonstrate the import of transgene DNA into the mitochondrial matrix in living mammalian cells. The unavailability of a mitochondria-specific reporter plasmid designed for mitochondrial expression severely hampers current efforts toward the development of effective mitochondrial expression vectors. Although any new nonviral transfection system (i.e., cationic lipids, polymers, and others) aimed at the nuclear-cytosolic expression of proteins can be systematically tested and subsequently improved by utilizing anyone of many commercially available reporter gene systems, such a methodical approach to develop mitochondrial transfection systems is currently impossible. 

The transcription and translation of mtDNA encoded proteins involves several mitochondria-specific proteins, in which defects also lead to combined OXPHOS enzyme deficiencies (21, 22). A special class of defects are those leading to a CoQio deficiency. The biosynthesis of CoQio is a multistep process that has been completely elucidated in yeast. In humans, several steps of this process have been shown to exist as well, and three different genetic defects in this pathway have been identified to date (23). 

Aliev G, Palacios HH, Cacabelos P, Cacabelos R, Burzynski G, Burzynski SR (2013) Mitochondria specific antioxidants and their derivatives in the context of the drug development for neurodegeneration and cancer. Drug Des 2 1. doi 10.4172/2169-0138.1000103... 

C. M. Porteous, A. Logan, C. Evans, E. C. Ledgerwood, D. K. Menon, F. Aigbiihio, R. A. Smith, and M. P. Murphy, Rapid uptake of lipophihc triphenylphosphonium cations by mitochondria in vivo following intravenous injection imphcations for mitochondria-specific therapies and probes. Biochim. Biophys. Acta., 1800 (2010) 1009-17. 

Fig. 9.9 2-Benzothienyl-pridine iridium cation 9.52 as a mitochondria-specific oxygen sensor [102]...

The phosphorescence of the 2-benzothienylpridine iridium cation 9.52 was significantly quenched by molecular oxygen in living cells, demonstrating that 2-benzothienylpridine iridium cation 9.52 can be used as a mitochondria-specific oxygen sensor as shown in Fig. 9.9 [102]. 

Mclachlan A, Kekre N, McNulty J, Pandey S (2005) Pancratistatin a natural anti-cancer compound that targets mitochondria specifically in cancer cells to induce apoptosis. Apoptosis 10 619... 

Actually, the eventual conversion of the free-living bacterium into an integrated part of the eukaryote cells involves, as we know, a transfer to the nucleus of most templates necessary for the synthesis of respiratory enzymes. Such transfer of original functions drastically cuts down the mitochondrial DNA to a mere vestige of the ancestral bacterial DNA. Although the remaining DNA is distinctly of bacterial type, it contains space only to template for a few proteins and some mitochondria-specific RNAs. 

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