Iyer 2008 Nature Precedings
|Iyer S, Thomas R, Portell F, Dunham L, Quigley C, Bennett JP (2008) Recombinant mitochondrial transcription factor A with N-terminal mitochondrial transduction domain increases respiration and mitochondrial gene expression in G11778A leber’s hereditary optic neuropathy cybrid cells. Nature Precedings: hdl:10101/npre.2008.2084.1|
Abstract: Diseases involving mitochondrial defects usually manifest themselves in highenergy, post-mitotic tissues such as brain, retina, skeletal and cardiac muscle and frequently cause deficiencies in mitochondrial bioenergetics1, 2. We have developed a scalable procedure to produce recombinant human mitochondrial transcription factor A (TFAM) 3-5 modified with an N-terminal protein transduction domain (PTD)6 and mitochondrial localization signal (MLS) that allow it to cross membranes and enter mitochondria through its “mitochondrial transduction domain” (MTD,=PTD+MLS). In vitro studies in a classic mitochondrial disease cell model demonstrated that Alexa488-labeled MTD-TFAM rapidly entered the mitochondrial compartment. MTD-TFAM treatment of these cell lines reversibly increased oxygen consumption (respiration) rates 3-fold, levels of respiratory proteins and mitochondrial gene expression. In vivo results demonstrated that respiration increased to lesser degrees in mitochondria from tissues of mice injected with MTD-TFAM. MTD-TFAM can alter mitochondrial bioenergetics and holds promise for treatment of mitochondrial diseases involving deficiencies of energy production.
• Keywords: TFAM, Respiration, Mitochondrial gene expression, Respiratory proteins
Labels: MiParea: Respiration, Genetic knockout;overexpression, mt-Medicine Pathology: Inherited
Tissue;cell: Nervous system
Coupling state: OXPHOS