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Jash S.,Indian Institute Of Chemical Biology Csir | Adhya S.,Indian Institute Of Chemical Biology Csir
Mitochondrion | Year: 2011

Many human diseases are associated with mutations and deletions in mitochondrial DNA (mtDNA). We have generated a cell line, EB delta1, with multiple mtDNA deletions, that is respiration-defective and generates high levels of superoxide, a reactive oxygen species. Treatment of EB delta1 with tagged polycistronic (pc) RNAs, encoding parts of the mitochondrial proteome, bound to a multi-subunit carrier complex, resulted in cellular uptake and transfer of the RNA to mitochondria, restoration of respiration, and suppression of superoxide levels. These findings have implications for correction of mitochondrial defects in age-related disorders due to mtDNA mutations. © 2011 Elsevier B.V. and Mitochondria Research Society. Source


Mahato B.,Indian Institute Of Chemical Biology Csir | Jash S.,Indian Institute Of Chemical Biology Csir | Adhya S.,Indian Institute Of Chemical Biology Csir
Mitochondrion | Year: 2011

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 ~. 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. Source


Jash S.,Indian Institute Of Chemical Biology Csir | Chowdhury T.,Indian Institute Of Chemical Biology Csir | Adhya S.,Indian Institute Of Chemical Biology Csir
Mitochondrion | Year: 2012

Genetic dysfunction of mitochondria is pathological, but an effective method of nucleic acid delivery to mitochondria in vivo is lacking. Injection into rodents of tagged polycistronic RNAs (pcRNAs) encoding parts of the organelle genome and bound to a carrier complex, resulted in rapid uptake and concentration of the RNA in many tissues. The delivered RNA was localized to mitochondria. A pan-genomic cocktail of pcRNAs restored mRNA levels, stimulated mitochondrial translation and respiratory capacity of skeletal muscle of middle-aged and old rats. Thus, the carrier-based protocol may be suitable for delivery of functional RNAs to mitochondria in vivo. © 2011 Elsevier B.V. and Mitochondria Research Society. Source

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