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

» Nature Precedings : hdl:10101/npre.2008.2084.1

Iyer S, Thomas R, Portell F, Dunham L, Quigley C, Bennett JP (2008) Nature Prec.

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

Labels:

Stress:Genetic Defect; Knockdown; Overexpression"Genetic Defect; Knockdown; Overexpression" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. 

Tissue;cell: Neurons; Brain"Neurons; Brain" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property. 

Regulation: Respiration; OXPHOS; ETS Capacity"Respiration; OXPHOS; ETS Capacity" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property. 

HRR: Oxygraph-2k