Effects of axon branching and asymmetry between the branches on transport, mean age, and age density distributions of mitochondria in neurons: A computational study,International Journal for Numerical Methods in Biomedical Engineering

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Effects of axon branching and asymmetry between the branches on transport, mean age, and age density distributions of mitochondria in neurons: A computational study
International Journal for Numerical Methods in Biomedical Engineering ( IF 2.2 ) Pub Date : 2022-09-20 , DOI: 10.1002/cnm.3648
Ivan A Kuznetsov _{1,

2} , Andrey V Kuznetsov ₃

Affiliation

We report a computational study of mitochondria transport in a branched axon with two branches of different sizes. For comparison, we also investigate mitochondria transport in an axon with symmetric branches and in a straight (unbranched) axon. The interest in understanding mitochondria transport in branched axons is motivated by the large size of arbors of dopaminergic neurons, which die in Parkinson's disease. Since the failure of energy supply of multiple demand sites located in various axonal branches may be a possible reason for the death of these neurons, we were interested in investigating how branching affects mitochondria transport. Besides investigating mitochondria fluxes between the demand sites and mitochondria concentrations, we also studied how the mean age of mitochondria and mitochondria age densities depend on the distance from the soma. We established that if the axon splits into two branches of unequal length, the mean ages of mitochondria and age density distributions in the demand sites are affected by how the mitochondria flux splits at the branching junction (what portion of mitochondria enter the shorter branch and what portion enter the longer branch). However, if the axon splits into two branches of equal length, the mean ages and age densities of mitochondria are independent of how the mitochondria flux splits at the branching junction. This even holds for the case when all mitochondria enter one branch, which is equivalent to a straight axon. Because the mitochondrial membrane potential (which many researchers view as a proxy for mitochondrial health) decreases with mitochondria age, the independence of mitochondria age on whether the axon is symmetrically branched or straight (providing the two axons are of the same length), and on how the mitochondria flux splits at the branching junction, may explain how dopaminergic neurons can sustain very large arbors and still maintain mitochondrial health across branch extremities.

中文翻译：

轴突分支和分支之间的不对称对神经元线粒体运输、平均年龄和年龄密度分布的影响：一项计算研究

我们报告了具有两个不同大小分支的分支轴突中线粒体运输的计算研究。为了进行比较，我们还研究了具有对称分支的轴突和直（无分支）轴突中的线粒体运输。人们对了解分支轴突中线粒体运输的兴趣是由于多巴胺能神经元的大尺寸乔木引起的，这些神经元在帕金森病中死亡。由于位于各个轴突分支的多个需求位点的能量供应失败可能是这些神经元死亡的可能原因，因此我们有兴趣研究分支如何影响线粒体运输。除了研究需求位点之间的线粒体通量和线粒体浓度之外，我们还研究了线粒体的平均年龄和线粒体年龄密度如何取决于距体体的距离。我们确定，如果轴突分裂成两个长度不等的分支，则线粒体的平均年龄和需求位点的年龄密度分布会受到线粒体通量在分支连接处如何分裂的影响（线粒体的哪些部分进入较短的分支以及哪些部分进入较短的分支）部分进入较长的分支）。然而，如果轴突分裂成两个长度相等的分支，则线粒体的平均年龄和年龄密度与线粒体通量在分支连接处如何分裂无关。这甚至适用于所有线粒体进入一个分支（相当于一根直轴突）的情况。由于线粒体膜电位（许多研究人员将其视为线粒体健康的指标）随着线粒体年龄的增长而降低，因此线粒体年龄与轴突是否对称分支或直（前提是两个轴突长度相同）无关线粒体通量如何在分支连接处分裂，可以解释多巴胺能神经元如何维持非常大的乔木，并仍然保持分支四肢的线粒体健康。

更新日期：2022-09-20

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