Iyer 2012 Hum Gene Ther: Difference between revisions
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{{Publication | {{Publication | ||
|title=Iyer S, Bergquist K, Young K, Gnaiger E, Rao RR, Bennett JP Jr (2012) Mitochondrial gene therapy improves respiration, biogenesis and transcription in G11778A Leberβs hereditary optic neuropathy and T8993G Leighβs syndrome cells. Hum Gene Ther 23: 647- | |title=Iyer S, Bergquist K, Young K, Gnaiger E, Rao RR, Bennett JP Jr (2012) Mitochondrial gene therapy improves respiration, biogenesis and transcription in G11778A Leberβs hereditary optic neuropathy and T8993G Leighβs syndrome cells. Hum Gene Ther 23:647-57. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/22390282 PMID: 22390282] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/22390282 PMID: 22390282 Open Access] | ||
|authors=Iyer S, Bergquist K, Young K, Gnaiger | |authors=Iyer S, Bergquist K, Young K, Gnaiger Erich, Rao RR, Bennett JP | ||
|year=2012 | |year=2012 | ||
|journal=Hum Gene Ther | |journal=Hum Gene Ther | ||
|abstract=Many incurable mitochondrial disorders result from mutant mitochondrial DNA (mtDNA) and impaired respiration. Leighβs syndrome (LS) is a fatal neurodegenerative disorder of infants and Leberβs 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. Leighβs syndrome (LS) is a fatal neurodegenerative disorder of infants and Leberβs 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, Leighβs syndrome, LHON disease, | |keywords=TFAM, mtDNA, Leighβs syndrome, LHON disease, Mitochondrial respiration, Biogenesis, Transcription, Diseased fibroblast, Cybrid cells | ||
|mipnetlab=US VA Richmond Bennett JP, AT Innsbruck Gnaiger E | |mipnetlab=US VA Richmond Iyer S, US VA Richmond Bennett JP, AT Innsbruck Gnaiger E, AT Innsbruck MitoCom | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
| | |area=Respiration, mt-Biogenesis;mt-density, Genetic knockout;overexpression, mt-Medicine | ||
|diseases=Inherited | |||
|organism=Human | |organism=Human | ||
|tissues=Fibroblast | |tissues=Fibroblast | ||
|preparations=Intact | |preparations=Intact cells | ||
| | |couplingstates=OXPHOS | ||
|instruments=Oxygraph-2k | |||
}} | }} | ||
* [http://www.news.vcu.edu/news/Researchers_Study_and_Develop_Approach_to_Treat_Mitochondrial Highlights on the VCU-News: Researchers Study and Develop Approach to Treat Mitochondrial Disorders]. | * [http://www.news.vcu.edu/news/Researchers_Study_and_Develop_Approach_to_Treat_Mitochondrial Highlights on the VCU-News: Researchers Study and Develop Approach to Treat Mitochondrial Disorders]. |
Latest revision as of 03:51, 23 November 2021
Iyer S, Bergquist K, Young K, Gnaiger E, Rao RR, Bennett JP Jr (2012) Mitochondrial gene therapy improves respiration, biogenesis and transcription in G11778A Leberβs hereditary optic neuropathy and T8993G Leighβs syndrome cells. Hum Gene Ther 23:647-57. |
Iyer S, Bergquist K, Young K, Gnaiger Erich, Rao RR, Bennett JP (2012) Hum Gene Ther
Abstract: Many incurable mitochondrial disorders result from mutant mitochondrial DNA (mtDNA) and impaired respiration. Leighβs syndrome (LS) is a fatal neurodegenerative disorder of infants and Leberβs 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. β’ Keywords: TFAM, mtDNA, Leighβs syndrome, LHON disease, Mitochondrial respiration, Biogenesis, Transcription, Diseased fibroblast, Cybrid cells
β’ 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 Tissue;cell: Fibroblast Preparation: Intact cells
Coupling state: OXPHOS
HRR: Oxygraph-2k