PDF(Pubmed)
Abstract：
Changes in mitochondrial distribution are a feature of numerous age-related neurodegenerative diseases. In Drosophila, reducing the activity of Cdk5 causes a neurodegenerative phenotype and is known to affect several mitochondrial properties. Therefore, we investigated whether alterations of mitochondrial distribution are involved in Cdk5-associated neurodegeneration. We find that reducing Cdk5 activity does not alter the balance of mitochondrial localization to the somatodendritic versus axonal neuronal compartments of the mushroom body, the learning and memory center of the Drosophila brain. We do, however, observe changes in mitochondrial distribution at the axon initial segment (AIS), a neuronal compartment located in the proximal axon involved in neuronal polarization and action potential initiation. Specifically, we observe that mitochondria are partially excluded from the AIS in wild-type neurons, but that this exclusion is lost upon reduction of Cdk5 activity, concomitant with the shrinkage of the AIS domain that is known to occur in this condition. This mitochondrial redistribution into the AIS is not likely due to the shortening of the AIS domain itself but rather due to altered Cdk5 activity. Furthermore, mitochondrial redistribution into the AIS is unlikely to be an early driver of neurodegeneration in the context of reduced Cdk5 activity.
摘要：
线粒体分布的变化是许多与年龄相关的神经退行性疾病的特征。在果蝇中,降低Cdk5的活性会导致神经变性表型，并且已知会影响几种线粒体特性。因此,我们研究了线粒体分布的改变是否与Cdk5相关的神经变性有关。我们发现，降低Cdk5活性不会改变线粒体定位的平衡蘑菇体的轴突神经元区室，果蝇大脑的学习和记忆中心。我们有,然而,观察轴突初始段(AIS)线粒体分布的变化，位于近端轴突的神经元区室，参与神经元极化和动作电位的启动。具体来说,我们观察到线粒体在野生型神经元中被部分排除在AIS之外，但是这种排除在Cdk5活性降低后就消失了，伴随着已知在这种情况下发生的AIS域的收缩。这种线粒体重新分布到AIS中不可能是由于AIS结构域本身的缩短,而是由于Cdk5活性的改变。此外，在Cdk5活性降低的情况下，线粒体再分布到AIS中不太可能是神经变性的早期驱动因素。
