Recombinant mitochondrial transcription factor A with N-terminal mitochondrial transduction domain increases respiration and mitochondrial gene expression

We developed a scalable procedure to produce human mitochondrial transcription factor A (TFAM) modified with an N-terminal protein transduction domain (PTD) and mitochondrial localization signal (MLS) that allow it to cross membranes and enter mitochondria through its "mitochondrial transductio...

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Bibliographic Details
Published in:Mitochondrion 2009-06, Vol.9 (3), p.196-203
Main Authors: Iyer, Shilpa, Thomas, Ravindar R, Portell, Francisco R, Dunham, Lisa D, Quigley, Caitlin K, Bennett, Jr, James P
Format: Article
Language:English
Subjects:
Adult
Bioenergetics
Cell Line
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Gene Expression
Genes, Mitochondrial
Humans
Male
Mitochondria - metabolism
Mitochondrial Proteins - biosynthesis
Mitochondrial Proteins - genetics
Mitochondrial Proteins - metabolism
Protein Sorting Signals
Protein Transport
Respiration
Transcription Factors - genetics
Transcription Factors - metabolism
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Description
Summary:We developed a scalable procedure to produce human mitochondrial transcription factor A (TFAM) modified with an N-terminal protein transduction domain (PTD) and mitochondrial localization signal (MLS) that allow it to cross membranes and enter mitochondria through its "mitochondrial transduction domain" (MTD=PTD+MLS). Alexa488-labeled MTD-TFAM rapidly entered the mitochondrial compartment of cybrid cells carrying the G11778A LHON mutation. MTD-TFAM reversibly increased respiration and levels of respiratory proteins. In vivo treatment of mice with MTD-TFAM increased motor endurance and complex I-driven respiration in mitochondria from brain and skeletal muscle. MTD-TFAM increases mitochondrial bioenergetics and holds promise for treatment of mitochondrial diseases involving deficiencies of energy production.
ISSN:1567-7249
1872-8278
DOI:10.1016/j.mito.2009.01.012