Investigating the role of Myosin VI in quality control of mitochondria linked to Parkinson's disease pathology

我们的老龄化人口中，有相当大一部分人受到帕金森氏症、运动神经元或阿尔茨海默病等神经退行性疾病发病较晚的影响。更好地了解导致这些神经退行性疾病的原因将导致新的治疗和预防策略。现在越来越多的研究表明，帕金森氏症和其他形式的痴呆症是由用于控制线粒体质量的细胞通路缺陷引起的，线粒体是我们的细胞动力站。如果这种代谢途径和“旧”线粒体的替换不能正常运作，就会导致能量产生减少和受损线粒体堆积，最终在神经细胞中导致它们死亡。我们的研究重点是肌球蛋白VI，这是一种分子马达蛋白，可以沿着轨道将货物驱动到细胞中的特定位置，就像火车沿着铁路网行驶到特定目的地一样。货物在我们之前的研究中发现的特定适配器蛋白的帮助下连接到这个马达上。新的结果表明，这种运动蛋白被招募到受损的线粒体中，并可能在线粒体的翻转和质量控制中发挥作用。因此，我们希望确定肌球蛋白VI及其接头蛋白在清除受损线粒体的重要途径中的确切作用。这将开辟新的研究领域，可能指导未来的临床研究以及潜在诊断工具和可能的治疗策略的开发。

A significant proportion of our ageing population is affected by the late onset of neurodegenerative disorders such as Parkinson's, motor neuron or Alzheimer's disease. A better understanding of what causes these neurodegenerative diseases will lead to new therapeutic and preventive strategies. More and more research now suggests that Parkinson's disease and also other forms of dementia are caused by defects in a cellular pathway that is used to control the quality of mitochondria, our cellular power stations. If this turnover pathway and the replacement of 'old' mitochondria does not function properly, it can cause decreased energy production and the pile up of damaged mitochondria, which eventually in nerve cells causes them to die. Our research is focused on myosin VI, a molecular motor protein, which drives cargo along tracks to specific sites in the cell, rather like a train running along a railway network to its specific destinations. The cargo is hooked up to this motor with the help of specific adaptor proteins that we have previously identified in our research. New results show that this motor protein is recruited to damaged mitochondria and may play a role in their turn over and their quality control. We thus hope to identify the precise roles of myosin VI and its adaptor proteins in the pathway that is important for clearance of damaged mitochondria. This will open up new areas of research that may guide future clinical studies and the development of potential diagnostic tools and possible therapeutic strategies.