MITOCHONDRIAL FISSION AND NEURODEGENERATION

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。具体目标：线粒体是神经元能量供应的关键，以支持生命功能，例如离子泵和通道活性、突触传递和轴突/树突转运。线粒体功能的缺陷不可避免地导致神经元功能障碍或细胞死亡。此外，越来越多的证据表明，线粒体功能障碍是几种神经退行性疾病的基础。然而，不太清楚的是究竟是什么导致了这些线粒体损伤。线粒体是一种动态的细胞器，它经历着融合和分裂。线粒体分裂和融合必须平衡以实现正常的神经元功能，并且由发挥相反作用的大型动力蛋白相关GTP酶协调，例如动力蛋白相关蛋白1（Drp 1）调节线粒体分裂，而OPA 1的线粒体融合蛋白1和线粒体融合蛋白2（Mfn 1，2）是线粒体融合所需的。Mfn 2或OPA 1的遗传性功能丧失突变导致人类神经退行性疾病。

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. Specific Aims: Mitochondria are pivotal for neuronal energy supply to support vital functions e.g. ion pump and channel activity, synaptic transmission, and axonal/dendritic transport. Deficits in mitochondrial function inevitably result in neuronal dysfunction or cell death. Moreover, there is increasing evidence that mitochondrial dysfunction underlies several neurodegenerative disorders. Less clear, however, is what exactly causes these mitochondrial injuries. Mitochondria are dynamic organelles undergoing fusion and fission. Mitochondrial fission and fusion has to be balanced for normal neuronal function and is orchestrated by large dynamin-related GTPases that exert opposing effects e.g. Dynamin-related protein 1 (Drp1) regulates mitochondrial fission, while Mitofusin 1 and Mitofusin 2 (Mfn1, 2) of OPA1 is required for mitochondrial fusion. Hereditary loss-of-function mutations in Mfn 2 or OPA1 cause neurodegenerative disorders in humans.