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Iyer 2008 Nature Precedings

From Bioblast
Publications in the MiPMap
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

» Nature Precedings : hdl:10101/npre.2008.2084.1

Iyer Shilpa, Thomas R, Portell F, Dunham L, Quigley C, Bennett JP (2008) Nature Precedings

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

O2k-Network Lab: US_VA Richmond_Bennett JP, US VA Richmond Iyer S

Labels: MiParea: Respiration, Genetic knockout;overexpression, mt-Medicine  Pathology: Inherited 

Tissue;cell: Nervous system 

Coupling state: OXPHOS 

HRR: Oxygraph-2k