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Creatine kinase B deficient neurons exhibit an increased fraction of motile mitochondria

机译:肌酸激酶B缺乏的神经元表现出运动的线粒体分数增加

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Background Neurons require an elaborate system of intracellular transport to distribute cargo throughout axonal and dendritic projections. Active anterograde and retrograde transport of mitochondria serves in local energy distribution, but at the same time also requires input of ATP. Here we studied whether brain-type creatine kinase (CK-B), a key enzyme for high-energy phosphoryl transfer between ATP and CrP in brain, has an intermediary role in the reciprocal coordination between mitochondrial motility and energy distribution. Therefore, we analysed the impact of brain-type creatine kinase (CK-B) deficiency on transport activity and velocity of mitochondria in primary murine neurons and made a comparison to the fate of amyloid precursor protein (APP) cargo in these cells, using live cell imaging. Results Comparison of average and maximum transport velocities and global transport activity showed that CK-B deficiency had no effect on speed of movement of mitochondria or APP cargo, but that the fraction of motile mitochondria was significantly increased by 36% in neurons derived from CK-B knockout mice. The percentage of motile APP vesicles was not altered. Conclusion CK-B activity does not directly couple to motor protein activity but cells without the enzyme increase the number of motile mitochondria, possibly as an adaptational strategy aimed to enhance mitochondrial distribution versatility in order to compensate for loss of efficiency in the cellular network for ATP distribution.
机译:背景神经元需要精细的细胞内运输系统以将货物分布在整个轴突和树突状突起中。线粒体的主动顺行和逆行运输有助于局部能量分布,但同时也需要输入ATP。在这里,我们研究了脑型肌酸激酶(CK-B)是大脑中ATP和CrP之间高能磷酸基转移的关键酶,在线粒体运动性和能量分布之间的相互协调中是否具有中介作用。因此,我们分析了脑型肌酸激酶(CK-B)缺乏对原代小鼠神经元转运活性和线粒体速度的影响,并与这些细胞中淀粉样前体蛋白(APP)的命运进行了比较,细胞成像。结果比较平均运输速度和最大运输速度以及全球运输活动表明,CK-B缺乏对线粒体或APP货物的移动速度没有影响,但是运动性线粒体的比例在源自CK-B的神经元中显着增加了36%。 B基因敲除小鼠。运动的APP囊泡的百分比未改变。结论CK-B活性并不直接与运动蛋白活性耦合,但是没有酶的细胞会增加运动性线粒体的数量,这可能是一种旨在增强线粒体分布多功能性的适应性策略,以补偿细胞网络中ATP效率的损失。分配。

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