神经元中肌动蛋白细胞骨架对线粒体分裂的调节机制研究

线粒体是细胞的能量代谢与信号转导的核心。作为动态的细胞器，线粒体的功能依赖于分裂与融合的平衡。线粒体动态功能紊乱，尤其是线粒体分裂异常是导致神经退行性疾病的主要原因。迄今为止，线粒体分裂的具体作用机制尚不明确。我们的最新研究表明肌动蛋白细胞骨架对于哺乳动物线粒体分裂至关重要，同时暗示肌动蛋白通过调节线粒体钙离子摄取来调控线粒体分裂。在本项目中，我们将利用前期研究中建立的活细胞成像系统，以原代培养的小鼠海马神经元为研究模型，确定肌动蛋白调控线粒体分裂的作用机制，并在分子水平阐明阿兹海默症小鼠神经元中线粒体分裂过程的异常，以期为神经退行性疾病的治疗提供新的切入点。

Mitochondria play central roles in energy production and signal transduction in cells. Mitochondria are dynamic organelles that undergo constant fission and fusion, which is essential to their normal functions. Defects in mitochondrial dynamics are one of major causes in the pathophysiology of neurodegenerative diseases. Previous studies have shown that dysfunctions in mitochondrial fission lead to multiple neurodegenerative diseases, such as Alzheimer’s disease(AD), Parkinson’s disease(PD), Huntington’s disease(HD) and Amyotrophic lateral sclerosis(ALS). However, mechanisms of mitochondrial fission remain unclear. Our recent studies indicated that actin filaments played essential roles in mitochondrial fission in mammals. Moreover, our recent data suggested that actin filaments facilitated mitochondrial fission by modulating mitochondrial calcium uptake. Through these studies, we established a reliable live-cell imaging platform, enabling us to investigate the mechanisms of mitochondrial fission in both WT and AD mice neuronal model. Our aim is to shed mechanistic insights into effective treatments for neurodegenerative diseases.