Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Neurobiol Dis. 2012 Jan;45(1):362-8. doi: 10.1016/j.nbd.2011.08.022. Epub 2011 Aug 25.
Mitochondrial dysfunction plays an important role in the pathogenesis of neurodegenerative diseases, numerous other disease states and senescence. The ability to monitor reactive oxygen species (ROS) within tissues and over time in animal model systems is of significant research value. Recently, redox-sensitive fluorescent proteins have been developed. Transgenic flies expressing genetically encoded redox-sensitive GFPs (roGFPs) targeted to the mitochondria function as a useful in vivo assay of mitochondrial dysfunction and ROS. We have generated transgenic flies expressing a mitochondrial-targeted roGFP2, demonstrated its responsiveness to redox changes in cultured cells and in vivo and utilized this protein to discover elevated ROS as a contributor to pathogenesis in a characterized neurodegeneration mutant and in a model of mitochondrial encephalomyopathy. These studies identify the role of ROS in pathogenesis associated with mitochondrial disease and demonstrate the utility of genetically encoded redox sensors in Drosophila.
线粒体功能障碍在神经退行性疾病、许多其他疾病状态和衰老的发病机制中起着重要作用。能够监测组织内和动物模型系统中随时间推移的活性氧（ROS）具有重要的研究价值。最近，已经开发出了氧化还原敏感的荧光蛋白。表达遗传编码氧化还原敏感 GFP（roGFP）的转基因果蝇靶向线粒体，可作为线粒体功能障碍和 ROS 的有用体内测定方法。我们生成了表达线粒体靶向 roGFP2 的转基因果蝇，证明其对培养细胞和体内氧化还原变化的反应性，并利用该蛋白发现 ROS 升高是特征性神经退行性突变体和线粒体脑肌病模型发病机制的一个促成因素。这些研究确定了 ROS 在与线粒体疾病相关的发病机制中的作用，并证明了遗传编码氧化还原传感器在果蝇中的实用性。
