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具有多个分支结的对称和非对称轴突中的线粒体运输:计算研究。

Mitochondrial transport in symmetric and asymmetric axons with multiple branching junctions: a computational study.

机构信息

Perelman School of Medicine, University of PA, Philadelphia, PA, USA.

Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.

出版信息

Comput Methods Biomech Biomed Engin. 2024 Jul;27(9):1071-1090. doi: 10.1080/10255842.2023.2226787. Epub 2023 Jul 10.

Abstract

Mitochondrial aging has been proposed to be involved in a variety of neurodegenerative disorders, such as Parkinson's disease. Here, we explore the impact of multiple branching junctions in axons on the mean age of mitochondria and their age density distributions in demand sites. The study examined mitochondrial concentration, mean age, and age density distribution in relation to the distance from the soma. We developed models for a symmetric axon containing 14 demand sites and an asymmetric axon containing 10 demand sites. We investigated how the concentration of mitochondria changes when an axon splits into two branches at the branching junction. Additionally, we studied whether mitochondrial concentrations in the branches are affected by what proportion of mitochondrial flux enters the upper branch versus the lower branch. Furthermore, we explored whether the distributions of mitochondrial mean age and age density in branching axons are affected by how the mitochondrial flux splits at the branching junction. When the mitochondrial flux is unevenly split at the branching junction of an asymmetric axon, with a greater proportion of the flux entering the longer branch, the average age of mitochondria (system age) in the axon increases. Our findings elucidate the effects of axonal branching on the mitochondrial age.

摘要

线粒体衰老被认为与多种神经退行性疾病有关,如帕金森病。在这里,我们探讨了轴突中的多个分支连接对需求部位线粒体的平均年龄及其年龄密度分布的影响。该研究考察了与胞体距离相关的线粒体浓度、平均年龄和年龄密度分布。我们为包含 14 个需求部位的对称轴突和包含 10 个需求部位的不对称轴突建立了模型。我们研究了当分支连接处分叉成两个分支时,线粒体浓度如何变化。此外,我们研究了线粒体流进入上分支与下分支的比例如何影响分支轴突中分支的线粒体浓度。此外,我们还探讨了在分支连接处线粒体通量的分裂方式是否会影响分支轴突中线粒体平均年龄和年龄密度的分布。当线粒体流在不对称轴突的分支连接处以不均匀的方式分裂,且更多的流进入较长的分支时,轴突中线粒体的平均年龄(系统年龄)会增加。我们的研究结果阐明了轴突分支对线粒体年龄的影响。

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Effect of mitochondrial circulation on mitochondrial age density distribution.线粒体循环对线粒体年龄密度分布的影响。
Int J Numer Method Biomed Eng. 2023 Dec;39(12):e3770. doi: 10.1002/cnm.3770. Epub 2023 Sep 9.
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Computation of the mitochondrial age distribution along the axon length.计算沿着轴突长度的线粒体年龄分布。
Comput Methods Biomech Biomed Engin. 2023 Oct;26(13):1582-1594. doi: 10.1080/10255842.2022.2128784. Epub 2022 Oct 13.
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Optimizing mitochondrial maintenance in extended neuronal projections.优化延长神经元突起中线粒体的维持。
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