INHIBITION OF PROTEIN IMPORT INTO MITOCHONDRIA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们开始努力描述线粒体凋亡过程中事件的顺序，以更好地理解心脏病模型。线粒体与疾病之间的关系变得越来越重要，关于线粒体结构和功能以及我们的工作试图回答的可能治疗方法，仍然存在许多问题。我们要澄清的要点是（1）渗透性转变是否发生在细胞色素c释放之前或之后，以及（2）内膜是否在渗透性转变后“重塑”以促进细胞色素c释放，如Korsmeyer小组（与Carmen Mannella合作）所建议的那样。我们使用的细胞转染了道格绿色实验室生产的荧光细胞色素c融合蛋白。我们正在探索的另一个关键问题是线粒体肿胀的时间。目前的假设是，由于活性氧（ROS）对线粒体的损伤通常是由缺陷的电子传递产生的。目前正在研究渗透性转换、细胞色素c释放和细胞凋亡在ROS损伤中的作用。与帕金斯博士合作，我们正在通过EM断层扫描对扰动的线粒体进行结构分析。这项研究的设想，以显着帮助了解ROS损伤，细胞色素c释放和细胞凋亡过程中发生的结构改变的程度。 另一个项目是基于我们与Perkins博士最近在圣地亚哥举行的线粒体疾病会议上的新合作。.我们目前的假设是，由于活性氧（ROS）对线粒体的损伤通常是由缺陷的电子传递产生的。渗透性转换、细胞色素c释放和细胞凋亡在ROS损伤中的作用正在研究中。关于肌肉萎缩症，伊莫舍弗勒？的细胞培养模型系统的线粒体疾病正在应用。此外，来自乔治敦大学的Lee-Jun Wong的工作也有助于这些研究，他从线粒体疾病患者那里获得了活检样本。我们还没有获得线粒体的结构分析EM断层扫描。然而，这种3-D技术被设想为显着帮助理解ROS损伤和凋亡过程中发生的结构改变的程度。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We initiated efforts to characterize the sequence of events in mitochondria during apoptosis to better understand models of heart disease. The relationship between mitochondria and disease is becoming increasingly important, and numerous questions remain regarding mitochondrial structure and function and possible treatments that our work attempts to answer. The important points we are clarifying are (1) Whether the permeability transition occurs before or after cytochrome c release and (2) Whether the inner membrane "remodels" following the permeability transition to facilitate cytochrome c release as suggested by Korsmeyer's group (collaborating with Carmen Mannella). We are using cells transfected with fluorescent cytochrome c fusion proteins produced by Doug Green's lab. Another key issue we are exploring is the timing of mitochondrial swelling. A current hypothesis is that damage to mitochondria due to reactive oxygen species (ROS) is often generated by defective electron transport. The role of the permeability transition, cytochrome c release, and apoptosis in ROS damage are currently being investigated. In collaboration with Dr. Perkins, we are conducting a structural analysis of perturbed mitochondria by EM tomography. This study is envisioned to significantly aid in understanding the extent of structural alterations occurring during ROS damage, cytochrome c release, and apoptosis. Another project is based on our new collaboration with Dr. Perkins coming out of the recent meeting on Mitochondrial Diseases in San Diego. . Our current hypothesis is that damage to mitochondria due to reactive oxygen species (ROS) is often generated by defective electron transport. The role of the permeability transition, cytochrome c release, and apoptosis in ROS damage is being investigated. In relation to muscular dystrophy, Immo Scheffler?s cell culture model systems for mitochondrial diseases are being applied. In addition, the work of Lee-Jun Wong from Georgetown University who has biopsy samples from mitochondrial disease patients is aiding these studies. We have yet to acquire a structural analysis of mitochondria by EM tomography. However, this 3-D technique is envisioned to significantly aid an understanding as to the extent of structural alterations occurring during ROS damage and apoptosis.