Fis1 Regulation of Mitochondrial Fission

描述(申请人提供)：线粒体分裂或分裂的改变会造成严重的后果，甚至死亡。然而，造成这种情况的原因尚不清楚。据推测，线粒体有自己的生命周期，包括分裂不健康的线粒体来移除它们。在这个模型中，适当的分裂平衡是至关重要的：分裂过多或受损都会导致不健康的线粒体。这个模型很有说服力，因为它解释了裂变的变化如何导致或促成许多根本不同的疾病，包括心脏病发作和中风的恢复，糖尿病引起的代谢压力增加，正常衰老，以及神经退行性疾病，如帕金森氏症和阿尔茨海默病。这项研究旨在了解负责线粒体裂变的多蛋白质机制是如何开启和关闭的。为了了解支配这一过程的蛋白质-蛋白质相互作用，生化和结构研究将与细胞生物学和遗传学方法相结合。更好地了解蛋白质机制及其工作原理将确定可能以小分子为靶点的调控关键点，以抑制和激活裂变。 这类分子的发现可能最终导致对以增强或受损的裂变为核心的疾病的治疗。

DESCRIPTION (provided by applicant): Altered division, or fission, of mitochondrial has severe consequences even death. Yet the reasons for this are unknown. It is postulated that the mitochondria have their own lifecycle that involves fission of unhealthy mitochondria to remove them. In this model the proper balance of fission is critical: either excess or impaired fission boh result in unhealthy mitochondria. This model is compelling because it explains how alterations in fission can cause or contribute to many fundamentally different diseases including recovery from heart attack and stroke, increased metabolic stress from diabetes, normal aging, and neurodegenerative diseases such as Parkinson's and Alzheimer's disease. This research is directed towards understanding how the multi-protein machinery that is responsible for mitochondrial fission is turned on and off. To understand the protein-protein interactions that govern this, biochemical and structural studies will be integrated with cell biological and genetic approaches. A better understanding of the protein machinery and how it works will identify key points of regulation that may be targeted with small molecules to inhibitor, and activate, fission. The discovery of such molecules may ultimately lead to treatments for diseases in which enhanced, or impaired, fission is central.