Recombinant mitochondrial transcription factor A with N-terminal mitochondrial transduction domain increases respiration and mitochondrial gene expression
| Autor: | Shilpa Iyer, James P. Bennett, Lisa D. Dunham, Ravindar R. Thomas, Francisco R. Portell, Caitlin K. Quigley |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Mitochondrial DNA Gene Expression Protein Sorting Signals Mitochondrion Biology MT-RNR1 Mitochondrial apoptosis-induced channel Article Cell Line Mitochondrial Proteins hemic and lymphatic diseases Humans neoplasms Molecular Biology Respiration Cell Biology TFAM Molecular biology Mitochondria respiratory tract diseases Cell biology DNA-Binding Proteins Protein Transport Genes Mitochondrial DNAJA3 Molecular Medicine Apoptosis-inducing factor ATP–ADP translocase therapeutics Transcription Factors |
| Zdroj: | Mitochondrion. 9:196-203 |
| ISSN: | 1567-7249 |
| DOI: | 10.1016/j.mito.2009.01.012 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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