Raju Raghavan, Jian Bixi, Hubbard William, Chaudry Irshad
Center for Surgical Research, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294.
Aging Dis. 2011 Apr 19;2(2):174-180.
Mitochondria are the major sites where energy is produced in the cell. Functions of organs such as the heart which has high energy demand are seriously affected by dysfunction of mitochondria. The functional changes in energy-dependent organs such as heart due to aging or any other cause are expected to be reflected in changes in expression of genes related to mitochondrial structure and function. Conversely, alteration of mitochondrial gene expression by any reason may also adversely affect function of organs such as heart that are energy-dependent. Molecular profiling of mitochondrial gene expression is therefore critical to understanding the mechanism of organ dysfunction. Mitochondrial structure and function are controlled by genes in the nuclear DNA and those in the mitochondrial DNA (mtDNA). The transcriptome from these two sources, together, contributing to the structure and function of mitochondria may be called mitoscriptome. This review elaborates on data gathered using a gene chip, RoMitochip, developed in our laboratory to study mitochondrial functional alteration in cardiomyocytes and left ventricular tissue following hypoxia or hemorrhagic injury. RoMitochip consists of probesets representing genes from nuclear DNA and mtDNA of both mice and rats. Our experiments using this chip in in vitro model of hypoxia and in vivo hemorrhagic injury model determined mitoscriptome signatures following hypoxia and hemorrhage, respectively. In addition, we also discuss past initiatives from other investigators that led to the development of microarray tools to profile mitoscriptome.
线粒体是细胞内产生能量的主要场所。像心脏这种对能量需求很高的器官,其功能会受到线粒体功能障碍的严重影响。由于衰老或任何其他原因,像心脏这样依赖能量的器官的功能变化,预计会反映在与线粒体结构和功能相关的基因表达变化上。相反,任何原因导致的线粒体基因表达改变,也可能对像心脏这样依赖能量的器官的功能产生不利影响。因此,线粒体基因表达的分子谱分析对于理解器官功能障碍的机制至关重要。线粒体的结构和功能由核DNA中的基因以及线粒体DNA(mtDNA)中的基因控制。来自这两个来源、共同促成线粒体结构和功能的转录组,可称为线粒体转录组。本综述详细阐述了使用我们实验室开发的基因芯片RoMitochip收集的数据,以研究缺氧或出血性损伤后心肌细胞和左心室组织中的线粒体功能改变。RoMitochip由代表小鼠和大鼠核DNA和mtDNA基因的探针组组成。我们在缺氧的体外模型和体内出血性损伤模型中使用该芯片进行的实验,分别确定了缺氧和出血后的线粒体转录组特征。此外,我们还讨论了其他研究人员过去的一些举措,这些举措促成了用于分析线粒体转录组的微阵列工具的开发。