Iyer 2012 Hum Gene Ther
|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.|
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
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