Difference between revisions of "Iyer 2012 Hum Gene Ther"
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|journal=Hum Gene Ther | |journal=Hum Gene Ther | ||
|abstract=Many incurable mitochondrial disorders result from mutant mitochondrial DNA (mtDNA) and impaired respiration. Leigh’s syndrome (LS) is a fatal neurodegenerative disorder of infants and Leber’s hereditary optic neuropathy (LHON) causes blindness in young adults. Treatment of LHON and LS cells respectively harboring G11778A and T8993G mutant mtDNA by >90%, with healthy donor mtDNA complexed with recombinant human mitochondrial transcription factor A (rhTFAM), improved mitochondrial respiration by ~1.2 fold in LHON cells and restored ~>50% ATP synthase function in LS cells. Mitochondrial replication, transcription and translation of key respiratory genes and proteins were increased in the short term. Increased NRF1, TFAMB1 and TFAMA expression alluded to the activation of mitochondrial biogenesis as a mechanism for improving mitochondrial respiration. These results represent the development of a therapeutic approach for LHON and LS patients in the near future. | |abstract=Many incurable mitochondrial disorders result from mutant mitochondrial DNA (mtDNA) and impaired respiration. Leigh’s syndrome (LS) is a fatal neurodegenerative disorder of infants and Leber’s hereditary optic neuropathy (LHON) causes blindness in young adults. Treatment of LHON and LS cells respectively harboring G11778A and T8993G mutant mtDNA by >90%, with healthy donor mtDNA complexed with recombinant human mitochondrial transcription factor A (rhTFAM), improved mitochondrial respiration by ~1.2 fold in LHON cells and restored ~>50% ATP synthase function in LS cells. Mitochondrial replication, transcription and translation of key respiratory genes and proteins were increased in the short term. Increased NRF1, TFAMB1 and TFAMA expression alluded to the activation of mitochondrial biogenesis as a mechanism for improving mitochondrial respiration. These results represent the development of a therapeutic approach for LHON and LS patients in the near future. | ||
|keywords=TFAM, mtDNA, Leigh’s syndrome, LHON disease, | |keywords=TFAM, mtDNA, Leigh’s syndrome, LHON disease, Mitochondrial respiration, Biogenesis, Transcription, Diseased fibroblast, Cybrid cells | ||
|mipnetlab=US VA Richmond Iyer S, US VA Richmond Bennett JP, AT Innsbruck Gnaiger E, AT Innsbruck MitoCom | |mipnetlab=US VA Richmond Iyer S, US VA Richmond Bennett JP, AT Innsbruck Gnaiger E, AT Innsbruck MitoCom | ||
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Revision as of 13:17, 13 March 2015
Iyer S, Bergquist K, Young K, Gnaiger E, Rao RR, Bennett JP Jr (2012) Mitochondrial gene therapy improves respiration, biogenesis and transcription in G11778A Leber’s hereditary optic neuropathy and T8993G Leigh’s syndrome cells. Hum Gene Ther 23:647-57. |
Iyer S, Bergquist K, Young K, Gnaiger E, Rao RR, Bennett JP (2012) Hum Gene Ther
Abstract: Many incurable mitochondrial disorders result from mutant mitochondrial DNA (mtDNA) and impaired respiration. Leigh’s syndrome (LS) is a fatal neurodegenerative disorder of infants and Leber’s hereditary optic neuropathy (LHON) causes blindness in young adults. Treatment of LHON and LS cells respectively harboring G11778A and T8993G mutant mtDNA by >90%, with healthy donor mtDNA complexed with recombinant human mitochondrial transcription factor A (rhTFAM), improved mitochondrial respiration by ~1.2 fold in LHON cells and restored ~>50% ATP synthase function in LS cells. Mitochondrial replication, transcription and translation of key respiratory genes and proteins were increased in the short term. Increased NRF1, TFAMB1 and TFAMA expression alluded to the activation of mitochondrial biogenesis as a mechanism for improving mitochondrial respiration. These results represent the development of a therapeutic approach for LHON and LS patients in the near future. • Keywords: TFAM, mtDNA, Leigh’s syndrome, LHON disease, Mitochondrial respiration, Biogenesis, Transcription, Diseased fibroblast, Cybrid cells
• O2k-Network Lab: US VA Richmond Iyer S, US VA Richmond Bennett JP, AT Innsbruck Gnaiger E, AT Innsbruck MitoCom
Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Genetic knockout;overexpression, mt-Medicine
Pathology: Inherited
Organism: Human
Preparation: Intact cells
Coupling state: OXPHOS
HRR: Oxygraph-2k