Format

Send to

Choose Destination
See comment in PubMed Commons below
Hum Gene Ther. 2012 Jun;23(6):647-57. doi: 10.1089/hum.2011.177. Epub 2012 Apr 17.

Mitochondrial gene therapy improves respiration, biogenesis, and transcription in G11778A Leber's hereditary optic neuropathy and T8993G Leigh's syndrome cells.

Author information

1
Center for the Study of Biological Complexity, Life Sciences, Virginia Commonwealth University, Richmond, VA 23284-3020, USA. siyer@vcu.edu

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 harboring G11778A and T8993G mutant mtDNA, respectively, 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.

PMID:
22390282
PMCID:
PMC3392617
DOI:
10.1089/hum.2011.177
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Mary Ann Liebert, Inc. Icon for PubMed Central
    Loading ...
    Support Center