Effects of axon branching and asymmetry between the branches on transport, mean age, and age density distributions of mitochondria in neurons: A computational study.
Effects of axon branching and asymmetry between the branches on transport, mean age, and age density distributions of mitochondria in neurons: A computational study.
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DOI：
10.1002/cnm.3648
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发表时间：
2022-11
影响因子：
2.1
通讯作者：
Kuznetsov, Andrey, V
中科院分区：
文献类型：
--
作者：
Kuznetsov, Ivan A.;Kuznetsov, Andrey, V
关键词：
我们报告了一个计算研究线粒体运输的分支轴突有两个分支的不同大小。为了比较，我们还研究了对称分支轴突和直（无分支）轴突中的线粒体运输。了解分支轴突中线粒体运输的兴趣是由在帕金森病中死亡的多巴胺能神经元的大尺寸乔木激发的。由于位于不同轴突分支的多个需求部位的能量供应失败可能是这些神经元死亡的一个可能原因，因此我们有兴趣研究分支如何影响线粒体转运。除了调查线粒体通量之间的需求网站和线粒体浓度，我们还研究了如何线粒体的平均年龄和线粒体年龄密度依赖于距离的索马。我们确定，如果轴突分裂成两个不等长的分支，线粒体的平均年龄和年龄密度分布的需求网站的线粒体流量如何在分支交界处分裂（线粒体的哪一部分进入较短的分支和哪一部分进入较长的分支）的影响。然而，如果轴突分裂成两个等长的分支，线粒体的平均年龄和年龄密度与线粒体流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的情况，这相当于一个直的轴突。因为线粒体膜电位（许多研究人员将其视为线粒体健康的代表）随着线粒体年龄的增长而减少，线粒体年龄与轴突是对称分支还是直的无关（假设两个轴突具有相同的长度），以及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能够维持非常大的乔木，并仍然保持线粒体的健康跨越分支四肢。研究了具有相等和不同长度的两个分支的分支轴突中的线粒体运输。如果轴突分裂成两个等长的分支，线粒体的平均年龄与线粒体流量在分支连接处如何分裂无关。线粒体年龄与轴突是对称分支还是对称直轴无关，这可以解释多巴胺能神经元如何能够维持非常大的乔木，并在分支末端保持线粒体健康。
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. Mitochondria transport in a branched axon with two branches of equal and different lengths is studied. If the axon splits into two branches of equal length, the mean ages of mitochondria are independent of how the mitochondria flux splits at the branching junction. The independence of mitochondria age on whether the axon is symmetrically branched or straight may explain how dopaminergic neurons can sustain very large arbors and still maintain mitochondrial health across branch extremities.
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DOI：
10.1016/j.cub.2016.07.064
发表时间：
2016-10-10
期刊：
Current biology : CB
影响因子：
--
作者：
Lewis TL Jr;Turi GF;Kwon SK;Losonczy A;Polleux F
通讯作者：
Polleux F
DOI：
10.1016/j.biocel.2004.09.009
发表时间：
2005-05-01
影响因子：
4
作者：
Chinta, SJ;Andersen, JK
通讯作者：
Andersen, JK
影响因子：
6.1
作者：
Trushina, Eugenia
通讯作者：
Trushina, Eugenia
影响因子：
2.6
作者：
Metzler, Holger;Sierra, Carlos A.
通讯作者：
Sierra, Carlos A.
影响因子：
5.7
作者：
Vanhauwaert, Roeland;Bharat, Vinita;Wang, Xinnan
通讯作者：
Wang, Xinnan