Center for the Study of Neurodegenerative Diseases and The Morris K. Udall Parkinson's Disease Research Center of Excellence, University of Virginia, PO Box 800394, Charlottesville, VA 22908, United States.
Mitochondrion. 2009 Jun;9(3):196-203. doi: 10.1016/j.mito.2009.01.012. Epub 2009 Feb 4.
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.
我们开发了一种可扩展的程序，用于生产带有 N 端蛋白转导结构域（PTD）和线粒体定位信号（MLS）的人线粒体转录因子 A（TFAM），使其能够通过其“线粒体转导结构域”（MTD=PTD+MLS）穿过细胞膜并进入线粒体。Alexa488 标记的 MTD-TFAM 迅速进入携带 G11778A LHON 突变的细胞杂种的线粒体区室。MTD-TFAM 可逆地增加了呼吸作用和呼吸蛋白的水平。用 MTD-TFAM 对小鼠进行体内治疗可增加大脑和骨骼肌线粒体中运动耐力和复合物 I 驱动的呼吸作用。MTD-TFAM 增加了线粒体生物能量学，有望治疗涉及能量产生缺陷的线粒体疾病。
